Publications by authors named "Jason Lin"

91 Publications

The Utility of Acid-Fast Bacillus (AFB) and Fungal Cultures in Orthopaedic Infections.

Cureus 2022 Jul 7;14(7):e26639. Epub 2022 Jul 7.

Graduate Medical Education - Biostatistics, Good Samaritan Regional Medical Center, Corvallis, USA.

Introduction When diagnosing suspected orthopaedic-related infections, fungal and acid-fast bacilli (AFB) cultures are often obtained intraoperatively. These cultures are difficult and time-consuming to grow and increase healthcare costs. This study aimed to quantify the rate of positive AFB and fungal cultures in orthopaedic infections and to compare potential risk factors for a positive result.  Methods Orthopaedic surgical cases for suspected infection at one institution from March 2013 through December 2019 were included. Data were collected on patient demographics and procedure characteristics for patients with surgical AFB or fungal lab tests ordered on the day of surgery. Results Of the 813 patients for whom intraoperative AFB or fungal cultures were ordered, 3.8% (N=31) had a positive result. Of the 31 positive results, 30 were from fungal cultures and one was from AFB cultures. Patients with a positive versus negative culture result did not differ significantly by age, sex, American Society of Anesthesiologists (ASA) score, diabetes, obesity, or HIV/AIDS. In both unadjusted and adjusted analyses, peripheral vascular disease (PVD) was associated with higher odds of a positive fungal culture result (adjusted OR (aOR)=3.5, 95%CI=1.3-8.4). Likewise, in both unadjusted and adjusted models, a hand/foot operating region was associated with higher odds of a positive fungal culture result compared with all other regions (aOR=4.2, 95%CI=1.9-9.8). Conclusion Intraoperative fungal and AFB cultures may not need to be obtained except in orthopaedic surgical cases for hand or foot infections or in patients with PVD.
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http://dx.doi.org/10.7759/cureus.26639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357251PMC
July 2022

Effects of Hypercarbia on Lower Extremity Primary Total Joint Replacement Infections.

Cureus 2022 Jun 18;14(6):e26069. Epub 2022 Jun 18.

Orthopedic Surgery, Good Samaritan Regional Medical Center, Corvallis, USA.

Introduction: Prosthetic joint infection (PJI) is a serious complication after total joint replacement (TJR). Adequate wound oxygenation is critical for wound healing and infection prevention. As carbon dioxide (CO) is exchanged for oxygen (O) in the lungs, serum bicarbonate (HCO ) may be used as a marker for predicting relative serum O levels, and therefore, healing potential. No currently published literature explores the relationship between serum bicarbonate levels and PJI in TJR patients.

Methods: We performed this retrospective review of lower extremity TJR patients to determine whether the risk of PJI and wound complications within one year was correlated with hypercarbia, which was defined as a preoperative serum bicarbonate level >30 mEq/L.

Results: Out of 1,690 TJR procedures, 1.6% (N=27) had a PJI or superficial wound infection within one year postoperatively. The average preoperative serum bicarbonate was 26.9 (SD 2.6) among patients without PJI and 27.2 (SD 2.1) among patients with PJI (p=0.46). Hypercarbia was present in 9.2% of non-PJI patients and in 7.4% of PJI patients. The relative risk of PJI and wound complications did not differ for patients with vs without hypercarbia (RR = 0.79, 95% CI = 0.19-3.31, p=0.75).

Conclusion: The results of this study provide preliminary evidence that preoperative hypercarbia may not be correlated with an increase in the risk of PJI or wound complications. However, due to the rarity of both PJI and hypercarbia, a larger patient population is needed to ensure adequate power to detect clinically meaningful effect sizes.
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http://dx.doi.org/10.7759/cureus.26069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293259PMC
June 2022

Authenticated Semi-Quantum Key Distribution Protocol Based on W States.

Sensors (Basel) 2022 Jul 2;22(13). Epub 2022 Jul 2.

Master Program for Digital Health Innovation, College of Humanities and Sciences, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist., Taichung 406040, Taiwan.

In 2019, Wen et al. proposed authenticated semi-quantum key distribution (ASQKD) for identity and message using the teleportation of W states and GHZ-like states without pre-shared keys. However, the ASQKD protocol presents a vital issue in the teleportation of W states owing to its inappropriate design. Bob recovers the teleported W states without obtaining the position of the corresponding photons and then returns the recovered photons back to Alice. Hence, the teleportation of W states in Wen et al.'s ASQKD protocol was malfunctioning. Moreover, Wen et al.'s ASQKD protocol requires quantum memory, which strongly disobeys the definition of semi-quantum proposed by Boyer et al. Therefore, in this study, we discover the flaws of Wen et al.'s ASQKD protocol and propose an authenticated semi-quantum key distribution protocol. When compared to Wen et al.'s ASQKD protocol, the proposed ASQKD protocol has the following advantages: legal semi-quantum environment (i.e., does not require quantum memory), reduced quantum hardware requirement (i.e., based only on W states), does not involve classical cryptography (i.e., the hash function), and provided 1.6 times higher qubit efficiency.
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http://dx.doi.org/10.3390/s22134998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9269753PMC
July 2022

Impact of Surgical Rejuvenation on Visual Processing and Character Attribution of Periorbital Aging.

Plast Reconstr Surg 2022 Jun 24. Epub 2022 Jun 24.

Division of Plastic, Craniofacial, and Hand Surgery, Department of Surgery, Sidra Medicine and Weill Cornell Medical College-Qatar, Doha, Qatar.

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http://dx.doi.org/10.1097/PRS.0000000000009458DOI Listing
June 2022

Transcriptomic analysis reveals high ITGB1 expression as a predictor for poor prognosis of pancreatic cancer.

PLoS One 2022 1;17(6):e0268630. Epub 2022 Jun 1.

Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Chiba Cancer Center, Chiba, Japan.

Transcriptomic analysis of cancer samples helps identify the mechanism and molecular markers of cancer. However, transcriptomic analyses of pancreatic cancer from the Japanese population are lacking. Hence, in this study, we performed RNA sequencing of fresh and frozen pancreatic cancer tissues from 12 Japanese patients to identify genes critical for the clinical pathology of pancreatic cancer among the Japanese population. Additionally, we performed immunostaining of 107 pancreatic cancer samples to verify the results of RNA sequencing. Bioinformatics analysis of RNA sequencing data identified ITGB1 (Integrin beta 1) as an important gene for pancreatic cancer metastasis, progression, and prognosis. ITGB1 expression was verified using immunostaining. The results of RNA sequencing and immunostaining showed a significant correlation (r = 0.552, p = 0.118) in ITGB1 expression. Moreover, the ITGB1 high-expression group was associated with a significantly worse prognosis (p = 0.035) and recurrence rate (p = 0.028). We believe that ITGB1 may be used as a drug target for pancreatic cancer in the future.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0268630PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9159604PMC
June 2022

Barriers and motivators to specializing in geriatrics and strategies for recruitment: scoping review.

Gerontol Geriatr Educ 2022 May 23:1-17. Epub 2022 May 23.

Department of Internal Medicine, Division of Geriatrics, Virginia Commonwealth University, Richmond, Virginia, US.

While the barriers to specializing in geriatrics are known, motivators behind why medical trainees choose geriatrics are not as well understood. It is also unknown if recruitment strategies in the literature address these barriers and motivators. The aim of this systematic scoping review is to examine the current literature on recruitment strategies alongside motivators and barriers for specializing in geriatrics. Eligible articles for this scoping review either focused on motivators or barriers among trainees (medical students, resident-physicians, fellows) or recruitment strategies. A scoping search was conducted in MEDLINE, Embase, CINAHL, and PsychINFO. Data was extracted on article characteristics and themes. 88 of 2064 articles were eligible and included. Personal fulfillment emerged as the most common theme for motivators, contrary to prior studies that cite positive role modeling. Financial disincentive remained the most common barrier, followed by limited exposure and "futile" practice. Promising interventions beyond financial compensation include defining geriatrics better, emphasizing the high job satisfaction rates, increasing clinical exposure for medical students, and additional funding for academic centers to recruit academic geriatricians. Policymakers and medical educators should consider multiple strategies that target the motivators, as well as the barriers to pursuing geriatrics.
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http://dx.doi.org/10.1080/02701960.2022.2078814DOI Listing
May 2022

Electrophoresis of a highly charged fluid droplet in dilute electrolyte solutions: Analytical Hückel-type solution.

Electrophoresis 2022 Aug 12;43(15):1611-1616. Epub 2022 May 12.

Department of Chemical Engineering, National Taiwan University, Taipei, Taiwan.

An analytical formula is presented here for the electrophoresis of a dielectric or perfectly conducting fluid droplet with arbitrary surface potentials suspended in a very dilute electrolyte solution. In other words, when the Debye length (κ ) is very large, or κa 1, where κ is the electrolyte strength and a stands for the droplet radius. This formula can be regarded as an extension of the famous Hückel solution valid for weakly charged rigid particles to arbitrarily charged fluid droplets. The formula reduces successfully to the ones obtained by Booth for a dielectric droplet, and Ohshima for a perfectly conducting droplet, both under Debye-Hückel approximation valid for weakly charged droplets. Moreover, the formula is valid for a gas bubble and a rigid solid particle as well. Classic results obtained by Hückel for a rigid particle are reproduced as well. We found that for a dielectric droplet, the more viscous the droplet is, the faster it moves regardless of its surface potential, contrary to the intuition based on the purely hydrodynamic consideration. For a perfectly conducting liquid droplet, on the other hand, the situation is reversed: The less viscous the droplet is, the faster it moves. The presence or absence of the spinning electric driving force tangent to the droplet surface is found to be responsible for it. As a result, an axisymmetric exterior vortex flow surrounding the droplet is always present for a dielectric liquid droplet, and never there for a conducting liquid droplet.
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http://dx.doi.org/10.1002/elps.202200048DOI Listing
August 2022

Machine learning with imaging features to predict the expression of ITGAV, which is a poor prognostic factor derived from transcriptome analysis in pancreatic cancer.

Int J Oncol 2022 May 8;60(5). Epub 2022 Apr 8.

Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Chiba Cancer Center, Chiba 260‑8717, Japan.

Radiogenomics has attracted attention for predicting the molecular biological characteristics of tumors from clinical images, which are originally a collection of numerical values, such as computed tomography (CT) scans. A prediction model using genetic information is constructed using thousands of image features extracted and calculated from these numerical values. In the present study, RNA sequencing of pancreatic ductal adenocarcinoma (PDAC) tissues from 12 patients was performed to identify genes useful in evaluating clinical pathology, and 107 PDAC samples were immunostained to verify the obtained findings. In addition, radiogenomics analysis of gene expression was performed by machine learning using CT images and constructed prediction models. Bioinformatics analysis of RNA sequencing data identified integrin αV (ITGAV) as being important for clinicopathological factors, such as metastasis and prognosis, and the results of sequencing and immunostaining demonstrated a significant correlation (r=0.625, P=0.039). Notably, the ITGAV high‑expression group was associated with a significantly worse prognosis (P=0.005) and recurrence rate (P=0.003) compared with the low‑expression group. The ITGAV prediction model showed some detectability (AUC=0.697), and the predicted ITGAV high‑expression group was also associated with a worse prognosis (P=0.048). In conclusion, radiogenomics predicted the expression of ITGAV in pancreatic cancer, as well as the prognosis.
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http://dx.doi.org/10.3892/ijo.2022.5350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8997334PMC
May 2022

Diffusiophoresis in suspensions of highly charged soft particles.

Electrophoresis 2022 Mar 19. Epub 2022 Mar 19.

Department of Chemical Engineering, National Taiwan University, Taipei, Taiwan.

Diffusiophoresis phenomenon of aoft particles suspended in binary electrolyte solutions is explored theoretically in this study based on the spherical cell model, focusing on the chemiphoresis component in absence of diffusion potential. Both the electrostatic and hydrodynamic aspects of the boundary confinement, or steric effect, due to the presence of neighboring particles are examined extensively under various electrokinetic conditions. Significant local extrema are found in mobility profiles expressed as functions of the Debye length in general, synchronized with the strength of the motion-inducing double layer polarization. Moreover, a seemingly peculiar phenomenon is observed that the soft particles may move faster in more concentrated suspensions. The competition between the simultaneous enhancement of the motion-inducing electric driving force and the motion-retarding hydrodynamic drag force from the boundary confinement effect of the neighboring particles is found to be responsible for it. The above findings are also demonstrated experimentally in a very recent study on the diffusiophoretic motion of soft particles through porous collagen hydrogels. The results presented here are useful in various practical applications of soft particles like drug delivery.
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http://dx.doi.org/10.1002/elps.202100380DOI Listing
March 2022

Real-world, multicentre evaluation of the incidence and risk factors for non-susceptible Stenotrophomonas maltophilia isolates.

J Glob Antimicrob Resist 2022 03 9;28:282-287. Epub 2022 Feb 9.

University of Georgia College of Pharmacy, Savannah, Georgia.

Background: Stenotrophomonas maltophilia is a cause of infection most commonly in the opportunistic host. Trimethoprim-sulfamethoxazole and levofloxacin are considered first-line treatment agents. With reports of increasing resistance to these first-line agents, it is important to determine risk factors associated with a non-susceptible isolate.

Methods: This was a real-world, multicentre, retrospective case-control study from five centres in the southeast United States evaluating S. maltophilia. The primary outcome was risk factors associated with non-susceptibility of S. maltophilia isolates to ≥1 antimicrobial agents. Secondary outcomes include incidence of S. maltophilia non-susceptibility, all-cause mortality, and 30-day readmission rates.

Results: There were 325 patients included in the study. For the primary outcome, the only factor associated with non-susceptibility per univariate analysis was isolation from urine culture (13.3% vs. 5.4%; P = 0.014), whereas the presence of mechanical ventilation (37.7% vs. 21.5%) and intensive care unit admission (35.3% vs. 18.4%) were associated with susceptibility (P < 0.001). For the secondary outcomes, non-susceptibility was present in 49% of isolates with 43 of 325 (13.2%), 53 of 324 (16.4%), and 105 of 172 (61%) to TMP-SMX, levofloxacin, and ceftazidime, respectively. Resistance to chloramphenicol and tigecycline was observed among 5/26 and 11/16 of tested isolates, respectively. Sixty-six patients (20%) experienced all-cause, inpatient mortality (18% susceptible vs. 23% non-susceptible; P = 0.280) and 44 patients (17%) were readmitted within 30 days of discharge (16% susceptible vs. 18% non-susceptible; P = 0.673).

Conclusion: S. maltophilia non-susceptibility had a prevalence of ∼50% to at least one first-line or commonly used agent. More research is needed to delineate risk factors for non-susceptible isolates.
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http://dx.doi.org/10.1016/j.jgar.2022.02.001DOI Listing
March 2022

A deletion at the polled P locus alone is not sufficient to cause a polled phenotype in cattle.

Sci Rep 2022 02 8;12(1):2067. Epub 2022 Feb 8.

Department of Animal Science, University of CA - Davis, Davis, CA, USA.

Dehorning is a common practice in the dairy industry, but raises animal welfare concerns. A naturally occurring genetic mutation (P allele) comprised of a 212 bp duplicated DNA sequence replacing a 10-bp sequence at the polled locus is associated with the hornless phenotype (polled) in cattle. To test the hypothesis that the 10 bp deletion alone is sufficient to result in polled, a CRISPR-Cas9 dual guide RNA approach was optimized to delete a 133 bp region including the 10 bp sequence. Timing of ribonucleoprotein complex injections at various hours post insemination (hpi) (6, 8, and 18 hpi) as well as in vitro transcribed (IVT) vs synthetic gRNAs were compared. Embryos injected 6 hpi had a significantly higher deletion rate (53%) compared to those injected 8 (12%) and 18 hpi (7%), and synthetic gRNAs had a significantly higher deletion rate (84%) compared to IVT gRNAs (53%). Embryo transfers were performed, and bovine fetuses were harvested between 3 and 5 months of gestation. All fetuses had mutations at the target site, with two of the seven having biallelic deletions, and yet they displayed horn bud development indicating that the 10 bp deletion alone is not sufficient to result in the polled phenotype.
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http://dx.doi.org/10.1038/s41598-022-06118-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8825853PMC
February 2022

Suppression of non-small-cell lung cancer A549 tumor growth by an mtDNA mutation-targeting pyrrole-imidazole polyamide-triphenylphosphonium and a senolytic drug.

Cancer Sci 2022 Apr 16;113(4):1321-1337. Epub 2022 Feb 16.

Division of Cancer Genetics, Chiba Cancer Center Research Institute, Chiba, Japan.

Certain somatic mutations in mtDNA were associated with tumor progression and frequently found in a homoplasmic state. We recently reported that pyrrole-imidazole polyamide conjugated with the mitochondria-delivering moiety triphenylphosphonium (PIP-TPP) targeting an mtDNA mutation efficiently induced apoptosis in cancer cells with the mutation but not normal cells. Here, we synthesized the novel PIP-TPP, CCC-021-TPP, targeting ND6 14582A > G homoplasmic missense mutation that is suggested to enhance metastasis of non-small-cell lung cancer A549 cells. CCC-021-TPP did not induce apoptosis but caused cellular senescence in the cells, accompanied by a significant induction of antiapoptotic BCL-XL. Simultaneous treatment of A549 cells with CCC-021-TPP and the BCL-XL selective inhibitor A-1155463 resulted in apoptosis induction. Importantly, the combination induced apoptosis and suppressed tumor growth in an A549 xenografted model. These results highlight the potential of anticancer therapy with PIP-TPPs targeting mtDNA mutations to induce cell death even in apoptosis-resistant cancer cells when combined with senolytics.
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http://dx.doi.org/10.1111/cas.15290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990788PMC
April 2022

Lack of Charge Interaction in the Ion Binding Site Determines Anion Selectivity in the Sodium Bicarbonate Cotransporter NBCe1.

Int J Mol Sci 2022 Jan 4;23(1). Epub 2022 Jan 4.

Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.

The Na/HCO cotransporter NBCe1 is a member of SLC4A transporters that move HCO across cell membranes and regulate intracellular pH or transepithelial HCO transport. NBCe1 is highly selective to HCO and does not transport other anions; the molecular mechanism of anion selectivity is presently unclear. We previously reported that replacing Asp with a Glu (D555E) in NBCe1 induces increased selectivity to other anions, including Cl. This finding is unexpected because all SLC4A transporters contain either Asp or Glu at the corresponding position and maintain a high selectivity to HCO. In this study, we tested whether the Cl transport in D555E is mediated by an interaction between residues in the ion binding site. Human NBCe1 and mutant transporters were expressed in oocytes, and their ability to transport Cl was assessed by two-electrode voltage clamp. The results show that the Cl transport is induced by a charge interaction between Glu and Lys. The bond length between the two residues is within the distance for a salt bridge, and the ionic strength experiments confirm an interaction. This finding indicates that the HCO selectivity in NBCe1 is established by avoiding a specific charge interaction in the ion binding site, rather than maintaining such an interaction.
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http://dx.doi.org/10.3390/ijms23010532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8745181PMC
January 2022

Reply: Using Artificial Intelligence to Measure Facial Expression following Facial Reanimation Surgery.

Plast Reconstr Surg 2022 02;149(2):345e-346e

Division of Plastic Surgery, Department of Surgery, Sidra Medicine, Department of Surgery, Weill Cornell Medicine-Qatar, Doha, Qatar.

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http://dx.doi.org/10.1097/PRS.0000000000008757DOI Listing
February 2022

Graphene-like Carbon from Calcium Hydroxide.

ACS Omega 2021 Nov 10;6(46):31066-31076. Epub 2021 Nov 10.

Department of Chemistry and Biochemistry and Department of Materials Science and Engineering, The University of Texas at Dallas, 800 West Campbell Road, Richardson, Texas 75080, United States.

The development of inexpensive and environmentally friendly graphene-like carbon is critical for its integration into industrial products. This work highlights the production of graphene-like carbon structures from calcium hydroxide. The chemical vapor deposition conditions to grow graphitic carbon on a calcium hydroxide catalyst are reported. Acetylene, steam, and calcium hydroxide are used to grow a crumpled carbon morphology. The crumpled carbon resulted in a high surface area of 1276 m/g and high electrical conductivity (>10 S/m). Additionally, the significance and origin of the C 1s X-ray photoelectron spectroscopy (XPS) π-π* plasmon loss peak as it is related to high electrical conductivity is reported. A unique mechanism for the catalytic process involving calcium acetylide is proposed. Several deposition times, steam concentration, and catalyst morphology were tested to synthesize a variety of carbon morphologies from calcium-based materials. Crumpled carbon, hollow nanospheres, bamboo-like carbon nanotubes, multi-walled carbon nanotubes, and graphene fiber morphologies were all formed using calcium-based catalysts. Multiple reaction conditions, a scaled reaction (300 g), and catalyst recyclability were investigated. Calcium-based materials were then used as catalysts for the growth of other graphene-like carbons.
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http://dx.doi.org/10.1021/acsomega.1c04305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8613825PMC
November 2021

Elemental analysis by Metallobalance provides a complementary support layer over existing blood biochemistry panel-based cancer risk assessment.

PeerJ 2021 4;9:e12247. Epub 2021 Oct 4.

Graduate School of Medical and Pharmaceutical Sciences, Chiba University, Chiba, Japan.

Despite the benefit of early cancer screening, Japan has one of the lowest cancer screening rates among developed countries, possibly due to there being a lack of "a good test" that can provide sufficient levels of test sensitivity and accuracy without a large price tag. As a number of essential and trace elements have been intimately connected to the oncogenesis of cancer, Metallobalance, a recent development in elemental analysis utilizing the technique of inductively coupled plasma mass spectrometry has been developed and tested as a robust method for arrayed cancer risk screening. We have conducted case-control epidemiological studies in the prefecture of Chiba, in the Greater Tokyo Area, and sought to determine both Metallobalance screening's effectiveness for predicting pan-cancer outcomes, and whether the method is capable enough to replace the more conventional antigen-based testing methods. Results suggest that MB screening provides some means of classification potential among cancer and non-cancer cases, and may work well as a complementary method to traditional antigen-based tumor marker testing, even in situations where tumor markers alone cannot discernibly identify cancer from non-cancer cases.
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http://dx.doi.org/10.7717/peerj.12247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8496461PMC
October 2021

Analytical solution to dielectric droplet diffusiophoresis under Debye-Hückel approximation.

Electrophoresis 2022 02 9;43(3):495-500. Epub 2021 Nov 9.

Department of Chemical Engineering, National Taiwan University, Taipei, Taiwan.

A simple analytical formula is obtained for the diffusiophoresis of a dielectric fluid droplet in symmetric binary electrolyte solutions under Debye-Hückel approximation valid for weakly charged droplets. The chemiphoresis is found to yield negative mobilities most of the time for droplets of constant surface charge density, which implies that the droplets tend to move away from the source releasing ionic chemicals. This is undesirable in some practical applications like drug delivery with liposomes in terms of conveying the drug-carrying liposomes to the desired area in the human body releasing specific ionic chemicals utilizing the self-guiding nature of diffusiophoresis. The further involvement of the electrophoresis component, however, may change the scenario via the oriented electric field generated by the induced diffusion potential. The lesson here is that while the impact of the chemiphoresis component is determined by nature and uncontrollable, the electrophoresis component serves as an artificially adjustable factor via choosing droplets with the surface charge of appropriate sign in practical applications. The results here have potential use in practical applications such as drug delivery. The portable simple analytical formula is a powerful asset to experimental researchers and design engineers in colloid science and technology to facilitate their works.
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http://dx.doi.org/10.1002/elps.202100264DOI Listing
February 2022

Endoscopic Browlift in Patients With Receding Hairlines.

J Craniofac Surg 2022 Mar-Apr 01;33(2):615-619

Division of Plastic and Reconstructive Surgery, Department of Surgery, Mayo Clinic.

Abstract: Patients with receding or high hairlines have traditionally been considered unfavorable candidates for endoscopic brow lift as this can further lengthen the hairline. We analyzed outcomes in patients that underwent a novel endoscopic brow lift technique with placement of incisions and anchoring Endotine Forehead Devices (CoApt Systems Inc, Palo Alto, CA, USA) directly at the natural forehead crease lines, in an effort to minimize elevation of the hairline, whereas providing well-hidden scars. We retrospectively reviewed all patients who underwent this new Endotine and incision placement between 2016 and 2020. Preoperative and postoperative photographs of all patients were analyzed to determine the postoperative changes in brow elevation and forehead length proportion (defined as length from cranium to chin).The forehead length proportion was unchanged pre- and post-operatively, with no statistically significant differences noted (P = 0.48). The average brow position elevation ranged from 2.78 mm in the medial location to 5.05 mm in the lateral location. All patients were happy with their appearance and had improved visual fields postoperatively. The forehead scars healed well and were well hidden in forehead rhytids at long term follow-up.This novel endoscopic brow lift technique provides an option to utilize a minimally invasive approach in patients with receding hairline. With this technique, visible scars were minimized, whereas still being able to achieve reasonable brow elevation. Thus, our approach enables long term maintenance of brow elevation with inconspicuous scars in the forehead.
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http://dx.doi.org/10.1097/SCS.0000000000008156DOI Listing
April 2022

Detection of Baseline Emotion in Brow Lift Patients Using Artificial Intelligence.

Aesthetic Plast Surg 2021 12 27;45(6):2742-2748. Epub 2021 Sep 27.

Plastic Surgery Division, Department of Surgery, Plastic Surgery Resident PGY4, Mayo Clinic, Rochester, MN, 55905, USA.

Background: The widespread popularity of browlifts and blepharoplasties speaks directly to the importance that patients place on the periorbital region of the face. In literature, most esthetic outcomes are based on instinctive analysis of the esthetic surgeon, rather than on patient assessments, public opinions, or other objective means. We employed an artificial intelligence system to objectively measure the impact of brow lifts and associated rejuvenation procedures on the appearance of emotion while the patient is in repose.

Methods: We retrospectively identified all patients who underwent bilateral brow lift for visual field obstruction between 2006 and 2019. Images were analyzed using a commercially available facial expression recognition software package (FaceReader™, Noldus Information Technology BV, Wageningen, Netherlands). The data generated reflected the proportion of each emotion expressed for any given facial movement and the action units associated.

Results: A total of 52 cases were identified after exclusion. Pre-operatively, the angry, happy, sad, scared, and surprised emotion were detected on average of 13.06%, 1.68%, 13.06%, 3.53%, and 0.97% among all the patients, respectively. Post-operatively, the angry emotion average decreased to 5.42% (p=0.009). The happy emotion increased to 9.35% (p=0.0013), while the sad emotion decreased to 5.42%. The scared emotion remained relatively the same at 3.4%, and the surprised emotion increased to 2.01%; however, these were not statistically significant.

Conclusion: This study proposes a paradigm shift in the clinical evaluation of brow lift and other facial esthetic surgery, implementing an existing facial emotion recognition system to quantify changes in expression associated with facial surgery.

Level Of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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http://dx.doi.org/10.1007/s00266-021-02430-0DOI Listing
December 2021

The Goldilocks Procedure with and without Implant-Based Immediate Breast Reconstruction in Obese Patients: The Mayo Clinic Experience.

Plast Reconstr Surg 2021 10;148(4):703-716

From the Divisions of Plastic and Reconstructive Surgery and Departments of Surgery, Mayo Clinic Rochester, Jacksonville, and Scottsdale; and Mayo Clinic Alix School of Medicine.

Background: Obesity is a risk factor for complications in breast reconstruction. Thus, implant-based immediate breast reconstruction in obese women may be controversial. The authors analyzed obese patients who underwent skin-sparing mastectomy using Wise-pattern incisions (Goldilocks procedure) and compared outcomes between two groups: Goldilocks with immediate breast reconstruction and Goldilocks only.

Methods: A retrospective review was performed of patients with a body mass index of 30 kg/m2 or higher who underwent the Goldilocks procedure at the Mayo Clinic Health System from 2012 to 2019. Data were extracted from electronic medical records. Minor complications (partial-thickness wound dehiscence or flap necrosis, or tissue expander/implant malposition) and major complications (full-thickness wound dehiscence or flap necrosis, capsular contracture, tissue expander/implant explantation, or unplanned reoperation or readmission) were compared between groups. Patient-reported outcomes using BREAST-Q questionnaires were also assessed.

Results: One hundred five patients (181 breasts) were included. Mean ± SEM age and body mass index were 57.1 ± 10.4 years and 37.9 ± 5.8 kg/m2 for the Goldilocks-only group and 51.5 ± 1.1 years and 35.5 ± 0.4 kg/m2 for the Goldilocks with immediate breast reconstruction group, respectively. Median follow-up time was 15.1 months (interquartile range, 10.0 to 28.6 months). Overall, 96 breasts underwent the Goldilocks-only procedure and 85 Goldilocks with immediate breast reconstruction. Multivariable analyses revealed a higher rate of minor complications (adjusted hazard ratio, 2.83; 95 percent CI, 1.22 to 7.02) and major complications (adjusted hazard ratio, 2.26; 95 percent CI, 1.25 to 4.24) in the Goldilocks with immediate breast reconstruction group compared with the Goldilocks-only group, at any given time. Patient satisfaction was not statistically different between groups.

Conclusions: The Goldilocks procedure is a feasible breast reconstructive option in obese patients; however, when it is performed with immediate breast reconstruction, it is associated with higher rates of complications. For patients with a body mass index of 40 kg/m2 or greater, the authors recommend the Goldilocks-only procedure or delayed reconstruction.

Clinical Question/level Of Evidence: Therapeutic, III.
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http://dx.doi.org/10.1097/PRS.0000000000008362DOI Listing
October 2021

Mitochondria: Endosymbiont bacteria DNA sequence as a target against cancer.

Cancer Sci 2021 Dec 4;112(12):4834-4843. Epub 2021 Oct 4.

Division of Cancer Genetics, Chiba Cancer Center Research Institute, Chiba, Japan.

As the energy factory for the cell, the mitochondrion, through its role of adenosine triphosphate production by oxidative phosphorylation, can be regarded as the guardian of well regulated cellular metabolism; the integrity of mitochondrial functions, however, is particularly vulnerable in cancer due to the lack of superstructures such as histone and lamina folds to protect the mitochondrial genome from unintended exposure, which consequently elevates risks of mutation. In cancer, mechanisms responsible for enforcing quality control surveillance for identifying and eliminating defective mitochondria are often poorly regulated, and certain uneliminated mitochondrial DNA (mtDNA) mutations and polymorphisms can be advantageous for the proliferation, progression, and metastasis of tumor cells. Such pathogenic mtDNA aberrations are likely to increase and occasionally be homoplasmic in cancer cells and, intriguingly, in normal cells in the proximity of tumor microenvironments as well. Distinct characteristics of these abnormalities in mtDNA may provide a new path for cancer therapy. Here we discuss a promising novel therapeutic strategy, using the sequence-specific properties of pyrrole-imidazole polyamide-triphenylphosphonium conjugates, against cancer for clearing abnormal mtDNA by reactivating mitochondrial quality control surveillance.
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http://dx.doi.org/10.1111/cas.15143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645765PMC
December 2021

Rotational Ankle Fracture Dislocation With Associated Lisfranc Fracture.

Cureus 2021 Aug 13;13(8):e17148. Epub 2021 Aug 13.

Orthopedic Surgery, Good Samaritan Regional Medical Center, Corvallis, USA.

While ankle fractures most often result from a rotational injury, Lisfranc injuries are more commonly associated with an axial load on a plantarflexed foot. Due to differing mechanisms of injury, rotational ankle fractures with Lisfranc injuries are uncommon and rarely discussed in the literature. Here we present a case of a rotational ankle fracture-dislocation with a concomitant Lisfranc injury. The Lisfranc injury, which was ultimately treated nonoperatively, was discovered seven weeks after operative fixation of the ankle fracture. At the last follow-up nine months after the initial injury, the patient had mild midfoot soreness with activity but no evidence of deformity or arch collapse. Although no deformity was observed in our patient, missed Lisfranc injuries may result in significant functional deficits indicating the importance of recognizing the possibility of a dual injury.
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http://dx.doi.org/10.7759/cureus.17148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436998PMC
August 2021

A linear five-ring pyrrole-imidazole polyamide-triphenylphosphonium conjugate targeting a mitochondrial DNA mutation efficiently induces apoptosis of HeLa cybrid cells carrying the mutation.

Biochem Biophys Res Commun 2021 10 31;576:93-99. Epub 2021 Aug 31.

Division of Cancer Genetics, Chiba Cancer Center Research Institute, 666-2 Nitona-cho, Chuoh-ku, Chiba, Japan. Electronic address:

Somatic mutations in mitochondrial DNA may provide a new avenue for cancer therapy due to their associations to a number of cancers and a tendency of homoplasmicity. In consideration of mitochondrial features and its relatively small genome size, a nucleotide-based targeting approach is a considerably more promising option. To explore the efficacy of short linear N-methylpyrrole-N-methylimidazole polyamide (PI polyamide), we synthesized a five-ring short PI polyamide that provided sequence-specific homing for the A3243G mitochondrial mutation upon conjugation with triphenylphosphonium cation (TPP). This PI polyamide-TPP was able to induce cytotoxicity in HeLamtA3243G cybrid cells, while preserving preferential binding for oligonucleotides containing the A3243G motif from melting temperature assays. The PI polyamide-TPP also localized in the mitochondria in HeLamtA3243G cells and induced mitochondrial reactive oxygen species production, mitophagy and apoptosis in a mutation-specific fashion compared to the wild-type HeLamtHeLa cybrids; normal human dermal fibroblasts were also relatively unaffected to suggest discriminating selectivity for the mutant mitochondria, offering a novel outlook for cancer therapy via mitochondrial homing of short linear PIP-TPPs.
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http://dx.doi.org/10.1016/j.bbrc.2021.08.088DOI Listing
October 2021

Partition of Pectoralis Major Musculocutaneous Flap as a Salvage Procedure for Simultaneous Coverage of the Exposed Carotid Artery and Reconstruction of Cervical Esophagus.

Ann Plast Surg 2021 10;87(4):435-439

From the Department of Plastic Surgery, China Medical University Hospital, Taichung, Taiwan.

Background: In advanced pharyngoesophageal cancer patients, a critical event is represented by the failure of primary reconstruction with exposure of the carotid artery and partial or total defect of the cervical esophagus. For these high-risk patients, a partitioned pectoralis major musculocutaneous (PMMC) flap can prevent carotid blowout and provide skin for simultaneous esophageal reconstruction.

Methods: Twenty-six patients needing pharyngoesophageal reconstruction together with coverage of carotid artery exposure were included in this retrospective case series. The patients were treated with a partitioned PMMC flap, based on the branching pattern of the pectoral branch of the thoracoacromial artery and the perforators of the pectoralis major muscle, to simultaneously reconstruct the defect and provide coverage for the carotid artery.

Results: In 25 patients, the partitioned PMMC flap reconstructions resulted in complete wound healing without occurrence of carotid blowout syndrome or fistula formation. Minor complications as partial flap necrosis (7.7%) and strictures formation (7.7%) were recorded but did not compromise reconstruction. Twenty-two patients were able to adopt a semisolid diet, and 4 had recurrence of cancer.

Conclusions: The partitioned PMMC flap reconstruction represents a useful salvage solution to simultaneously restore the continuity of the alimentary tract and provide reliable coverage for the exposed carotid artery.
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http://dx.doi.org/10.1097/SAP.0000000000002895DOI Listing
October 2021

Predicting road quality using high resolution satellite imagery: A transfer learning approach.

PLoS One 2021 9;16(7):e0253370. Epub 2021 Jul 9.

Department of Applied Science, William & Mary, Williamsburg, VA, United States of America.

Recognizing the importance of road infrastructure to promote human health and economic development, actors around the globe are regularly investing in both new roads and road improvements. However, in many contexts there is a sparsity-or complete lack-of accurate information regarding existing road infrastructure, challenging the effective identification of where investments should be made. Previous literature has focused on overcoming this gap through the use of satellite imagery to detect and map roads. In this piece, we extend this literature by leveraging satellite imagery to estimate road quality and concomitant information about travel speed. We adopt a transfer learning approach in which a convolutional neural network architecture is first trained on data collected in the United States (where data is readily available), and then "fine-tuned" on an independent, smaller dataset collected from Nigeria. We test and compare eight different convolutional neural network architectures using a dataset of 53,686 images of 2,400 kilometers of roads in the United States, in which each road segment is measured as "low", "middle", or "high" quality using an open, cellphone-based measuring platform. Using satellite imagery to estimate these classes, we achieve an accuracy of 80.0%, with 99.4% of predictions falling within the actual or an adjacent class. The highest performing base model was applied to a preliminary case study in Nigeria, using a dataset of 1,000 images of paved and unpaved roads. By tailoring our US-model on the basis of this Nigeria-specific data, we were able to achieve an accuracy of 94.0% in predicting the quality of Nigerian roads. A continuous case estimate also showed the ability, on average, to predict road quality to within 0.32 on a 0 to 3 scale (with higher values indicating higher levels of quality).
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253370PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270213PMC
October 2021

MCT4 is induced by metastasis-enhancing pathogenic mitochondrial NADH dehydrogenase gene mutations and can be a therapeutic target.

Sci Rep 2021 06 25;11(1):13302. Epub 2021 Jun 25.

Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, 666-2 Nitona-cho, Chuoh-ku, Chiba, 260-8717, Japan.

Pathogenic mitochondrial NADH dehydrogenase (ND) gene mutations enhance the invasion and metastasis of various cancer cells, and they are associated with metastasis in human non-small cell lung cancer (NSCLC). Moreover, monocarboxylate transporter 4 (MCT4) is overexpressed in solid cancers and plays a role in cancer cell proliferation and survival. Here, we report that MCT4 is exclusively expressed in mouse transmitochondrial cybrids with metastasis-enhancing pathogenic ND6 mutations. A high level of MCT4 is also detected in human NSCLC cell lines and tissues predicted to carry pathogenic ND mutations and is associated with poor prognosis in NSCLC patients. MCT4 expression in the cell lines is suppressed by N-acetyl-L-cysteine. Phosphatidylinositol-3 kinase (PI3K), AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) are involved in the regulation of MCT4 expression in the transmitochondrial cybrid cells. An MCT1/4 inhibitor effectively kills NSCLC cells with predicted pathogenic ND mutations, but an MCT1/2 inhibitor does not have the same effect. Thus, MCT4 expression is augmented by pathogenic ND mutations and could be a biomarker and a therapeutic target in pathogenic ND mutation-harbouring metastatic tumours.
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http://dx.doi.org/10.1038/s41598-021-92772-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233425PMC
June 2021

Electroporation-Mediated Genome Editing of Livestock Zygotes.

Front Genet 2021 13;12:648482. Epub 2021 Apr 13.

Department of Animal Science, University of California, Davis, Davis, CA, United States.

The introduction of genome editing reagents into mammalian zygotes has traditionally been accomplished by cytoplasmic or pronuclear microinjection. This time-consuming procedure requires expensive equipment and a high level of skill. Electroporation of zygotes offers a simplified and more streamlined approach to transfect mammalian zygotes. There are a number of studies examining the parameters used in electroporation of mouse and rat zygotes. Here, we review the electroporation conditions, timing, and success rates that have been reported for mice and rats, in addition to the few reports about livestock zygotes, specifically pigs and cattle. The introduction of editing reagents at, or soon after, fertilization can help reduce the rate of mosaicism, the presence of two of more genotypes in the cells of an individual; as can the introduction of nuclease proteins rather than mRNA encoding nucleases. Mosaicism is particularly problematic in large livestock species with long generation intervals as it can take years to obtain non-mosaic, homozygous offspring through breeding. Gene knockouts accomplished the non-homologous end joining pathway have been more widely reported and successfully accomplished using electroporation than have gene knock-ins. Delivering large DNA plasmids into the zygote is hindered by the zona pellucida (ZP), and the majority of gene knock-ins accomplished by electroporation have been using short single stranded DNA (ssDNA) repair templates, typically less than 1 kb. The most promising approach to deliver larger donor repair templates of up to 4.9 kb along with genome editing reagents into zygotes, without using cytoplasmic injection, is to use recombinant adeno-associated viruses (rAAVs) in combination with electroporation. However, similar to other methods used to deliver clustered regularly interspaced palindromic repeat (CRISPR) genome-editing reagents, this approach is also associated with high levels of mosaicism. Recent developments complementing germline ablated individuals with edited germline-competent cells offer an approach to avoid mosaicism in the germline of genome edited founder lines. Even with electroporation-mediated delivery of genome editing reagents to mammalian zygotes, there remain additional chokepoints in the genome editing pipeline that currently hinder the scalable production of non-mosaic genome edited livestock.
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http://dx.doi.org/10.3389/fgene.2021.648482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078910PMC
April 2021

Instructional interventions for improving COVID-19 knowledge, attitudes, behaviors: Evidence from a large-scale RCT in India.

Soc Sci Med 2021 05 17;276:113846. Epub 2021 Mar 17.

Bitscopic, Inc., 715 Colorado Avenue Suite B, Palo Alto, CA, 94303, USA. Electronic address:

Seeking ways to encourage broad compliance with health guidelines during the pandemic, especially among youth, we test two hypotheses pertaining to the optimal design of instructional interventions for improving COVID-19-related knowledge, attitudes, and behaviors. We randomly assigned 8376 lower-middle income youth in urban India to three treatments: a concentrated and targeted fact-based, instructional intervention; a longer instructional intervention that provided the same facts along with underlying scientific concepts; and a control. Relative to existing efforts, we find that both instructional interventions increased COVID-19-related knowledge immediately after intervention. Relative to the shorter fact-based intervention, the longer intervention resulted in sustained improvements in knowledge, attitudes, and self-reported behavior. Instead of reducing attention and comprehension by youth, the longer scientific based treatment appears to have increased understanding and retention of the material. The findings are instrumental to understanding the design of instruction and communication in affecting compliance during this and future pandemics.
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http://dx.doi.org/10.1016/j.socscimed.2021.113846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963523PMC
May 2021

Matters of data openness and KapWeb, a web tool of multi-cancer survival analysis for cancer survivors.

Cancer Sci 2021 May 10;112(5):2060-2062. Epub 2021 Mar 10.

Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Chiba, Japan.

KapWeb is an interactive tool for the determination of cancer survival rates based on case outcomes compiled from more than half a million records from cancer registries all over Japan, and we believe that both the tool and the call for data openness and transparency are important.
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http://dx.doi.org/10.1111/cas.14788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088959PMC
May 2021

One-step generation of a targeted knock-in calf using the CRISPR-Cas9 system in bovine zygotes.

BMC Genomics 2021 Feb 12;22(1):118. Epub 2021 Feb 12.

Department of Animal Science, University of California - Davis, Davis, CA, USA.

Background: The homologous recombination (HR) pathway is largely inactive in early embryos prior to the first cell division, making it difficult to achieve targeted gene knock-ins. The homology-mediated end joining (HMEJ)-based strategy has been shown to increase knock-in efficiency relative to HR, non-homologous end joining (NHEJ), and microhomology-mediated end joining (MMEJ) strategies in non-dividing cells.

Results: By introducing gRNA/Cas9 ribonucleoprotein complex and a HMEJ-based donor template with 1 kb homology arms flanked by the H11 safe harbor locus gRNA target site, knock-in rates of 40% of a 5.1 kb bovine sex-determining region Y (SRY)-green fluorescent protein (GFP) template were achieved in Bos taurus zygotes. Embryos that developed to the blastocyst stage were screened for GFP, and nine were transferred to recipient cows resulting in a live phenotypically normal bull calf. Genomic analyses revealed no wildtype sequence at the H11 target site, but rather a 26 bp insertion allele, and a complex 38 kb knock-in allele with seven copies of the SRY-GFP template and a single copy of the donor plasmid backbone. An additional minor 18 kb allele was detected that looks to be a derivative of the 38 kb allele resulting from the deletion of an inverted repeat of four copies of the SRY-GFP template.

Conclusion: The allelic heterogeneity in this biallelic knock-in calf appears to have resulted from a combination of homology directed repair, homology independent targeted insertion by blunt-end ligation, NHEJ, and rearrangement following editing of the gRNA target site in the donor template. This study illustrates the potential to produce targeted gene knock-in animals by direct cytoplasmic injection of bovine embryos with gRNA/Cas9, although further optimization is required to ensure a precise single-copy gene integration event.
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http://dx.doi.org/10.1186/s12864-021-07418-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881600PMC
February 2021
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