bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polyethylene Glycol Fusion Restores Axonal Continuity and Improves Return of Function in a Rat Median Nerve Denervation Model
Authors: Frost Christopher , Salous Abdel , Ketheeswaran Suvethavarshini , Ngaage Ledibabari M. , Hanwright Philip J. , Ghergherehchi Cameron , Tuffaha Sami , Vaidya Dhananjay , Bittner George D. , Brandacher Gerald , Shores Jaimie T. 
Published: September 2023

Background:
Polyethylene glycol (PEG) can fuse severed closely apposed axolemmas and restore axonal continuity. The authors evaluated the effects of PEG fusion on functional recovery in a rodent forelimb model of peripheral nerve injury.

Methods:
The median nerves of male Lewis rats (n = 5 per group) were transected and repaired with standard suture repair (SR), SR with PEG (PEG), or SR with PEG and 1% methylene blue (PEG+MB); a sham surgery group was also included. Proximal stimulation produced compound nerve and muscle action potentials recorded distally. The contralateral limb of each animal acted as an internal control for grip strength measurements.

Results:
Compound nerve and muscle action potentials immediately returned in all PEG and PEG+MB animals, but not in SR animals. The PEG and PEG+MB groups demonstrated earlier return of function by postoperative day (POD) 7 (62.6 ± 7.3% and 50.9 ± 6.7% of contralateral limb grip strength, respectively) compared with the SR group, in which minimal return of function was not measurable until POD 21. At POD 98, the PEG group grip strength recovered to 77.2 ± 2.8% and the PEG+MB grip strength recovered to 79.9 ± 4.4%, compared with 34.9 ± 1.8% recovery in the SR group (P < 0.05). The PEG and PEG+MB groups reached 50% of the sham group grip strength on POD 3.8 and POD 6.3, respectively, whereas the SR group did not reach 50% grip strength recovery of the sham group throughout the study period.

Conclusion:
PEG fusion plus neurorrhaphy with or without MB reestablished axonal continuity, shortened recovery time, and augmented functional recovery compared with suture neurorrhaphy alone.

Clinical Relevance Statement:
PEG fusion with neurorrhaphy may bypass Wallerian degeneration, leading to augmented and shortened functional recovery.
Using the Neuromuscular Junction Cellular Response to Predict Functional Recovery after Nerve Grafting in a Mouse Experimental Model
Authors: Lu Johnny Chuieng-Yi , Huang Yu-Han , Chen Angela Chien-Yu , Chuang David Chwei-Chin 
Published: September 2023

Background:
Functional recovery following peripheral nerve injury worsens with increasing time of denervation before repair. Denervated muscle undergoes progressive atrophy that limits the extent to which motor endplates can be reinnervated. The aims of this study were to assess nerve injuries reconstructed at different time points and to identify various neural and muscle-based markers to predict functional outcome, including an in-depth look at the neuromuscular junction (NMJ).

Methods:
Adult wild-type C57BL/6J mice underwent surgery on the sciatic nerve and were divided into 5 groups: (1) nerve cut and repaired, (2) acute (nerve cut and immediately repaired with a 1-cm autograft), (3) subacute (nerve grafted 2 weeks after injury), (4) delayed (nerve grafted 4 weeks after injury), (5) nerve cut and capped. Functional recovery was measured by treadmill and electrodiagnostic tests. Nerves were harvested for histologic evaluation, and leg muscles, for histologic evaluation and NMJ immunofluorescent staining of motor endplate innervation and terminal Schwann cells (tSCs).

Results:
The delayed graft group performed worst in nearly all parameters. The subacute graft group shared more similarities with the acute group, especially the tSC response (subacute, 48%; acute, 51%) and motor endplate innervation pattern (subacute, 75%; acute, 72%). The only parameters to elucidate differences were muscle weight and motor endplate fragmentation. Traditional axon count failed to capture differences among the 3 groups.

Conclusion:
The tSC activity and NMJ innervation pattern can be used as predictive markers of functional recovery that capture differences among acute, subacute, and delayed nerve injuries.

Clinical Relevance Statement:
The tSC activity at the NMJ displayed by immunohistochemical methods can accurately reflect target muscle innervation over time. This can be used as a predictor of reinnervation when timing of nerve reconstruction is delayed, which can be a critically needed tool in clinical scenarios.
National Impact of SARS-CoV-2 Infection on HIV Virological Suppression in South Africa
Authors: Cassim Naseem , Hans Lucia , Venter W. D. Francois , Somayya Sarang , Da Silva Pedro , Stevens Wendy Susan 
Published: September 2023

Background:
Coronavirus disease (COVID-19) severely disrupted routine health care globally. This study assessed the impact of successive COVID-19 waves on HIV viral load (VL) suppression in South Africa, using the national public sector laboratory database. Guidelines recommend VL monitoring at 6 months after treatment initiation, annually once if suppressed, or more frequently if unsuppressed.

Methods:
Specimen-level VL data were extracted for the period January 2019–December 2021. We assessed the national percentage of samples with a VL <50 (virological suppression), 50–999 (low-level viremia), and ≥1000 (viremia) copies/mL. Data were analyzed by calendar year and month. Data for 2019 (pre–COVID-19) were compared with the 2020 and 2021 calendar years (lockdowns imposed). The national number of COVID-19 cases was reported to indicate the wave periods as follows: 1 (ancestral)-June–August 2020; 2 (Beta)-December 2020–January 2021; 3 (Delta)-June–August 2021, and 4 (Omicron)-December 2021.

Results:
Data are reported for 17,460,264 samples, with 5,608,733, 5,840,056, and 6,011,475 tests performed in 2019, 2020, and 2021 respectively. Overall, a VL of <50, 50–999, and ≥1000 copies/mL were reported for 69.4%, 17.3%, and 13.4% of samples, respectively. A VL <50 copies/mL was reported for 67.7%, 70.3%, and 70.0% of patients in 2019, 2020, and 2021, respectively. For the 2020 and 2021 calendar years, the monthly percentage of patients with a VL <50 copies/mL ranged between 64.6% and 72.7%.

Conclusion:
Our findings indicate that COVID-19 has not had a substantial impact on the percentage of samples with virological suppression at the national level.
Pudendal Nerve Block Analgesia at the Time of Vaginal Surgery: A Randomized, Double-Blinded, Sham-Controlled Trial
Authors: Slopnick Emily A. , Sears Sarah B. , Chapman Graham C. , Sheyn David D. , Abrams Megan K. , Roberts Kasey M. , Pollard Robert , Mangel Jeffrey 
Published: September 2023

Importance
Effective opioid-sparing postoperative analgesia requires a multimodal approach. Regional nerve blocks augment pain control in many surgical fields and may be applied to pelvic floor reconstruction.

Objective
This study aimed to evaluate the impact of pudendal nerve block on postoperative pain control and opioid consumption after vaginal surgery.

Study Design
In this randomized, double-blind, sham-controlled trial, we enrolled women undergoing pelvic reconstruction, excluding patients with chronic pelvic pain or contraindications to nonnarcotic analgesia. Patients were randomized to transvaginal pudendal nerve block (9 mL 0.25% bupivacaine and 1 mL 40 mg/mL triamcinolone) or sham injection (10 mL normal saline). Primary outcomes were pain scores and opioid requirements. Sixty patients were required to show a 20-mm difference on a 100-mm visual analog scale (VAS).

Results
We randomized 71 patients: 36 pudendal block and 35 sham. Groups were well matched in baseline characteristics and surgery type. Prolapse repairs were most common (n = 63 [87.5%]), and there was no difference in anesthetic dose or operative time. Pain scores were equivalent in the postanesthesia care unit (mean VAS, 53.1 [block] vs 56.4 [sham]; P = 0.517) and on postoperative day 4 (mean VAS, 26.7 [block] vs 35.5 [sham]; P = 0.131). On postoperative day 1, the intervention group reported less pain, but this did not meet our 20 mm goal for clinical significance (mean VAS, 29.2 vs 42.5; P = 0.047). A pudendal block was associated with lower opioid consumption at all time points, but this was not statistically significant.

Conclusions
Surgeon-administered pudendal nerve block at the time of vaginal surgery may not significantly improve postoperative pain control or decrease opioid use.
Objective Diplopia Outcomes for Patients Treated With Teprotumumab for Thyroid Eye Disease
Authors: Mudalegundi Shwetha , Huang Peng , Henderson Amanda D. , Carey Andrew R. 
Published: September 2023

Background:
Thyroid eye disease (TED) is a condition caused by inflammatory damage to the periocular tissue that often leads to double vision. Teprotumumab is an insulin-like growth factor 1 receptor antibody that was FDA approved for the management of TED in 2020, although much is yet to be elucidated regarding its effects on diplopia outcomes among patients with TED. Diplopia is a significant and life-altering effect of TED. Previous studies have reported the effect of teprotumumab on double vision subjectively using the Gorman diplopia score. However, there is a gap in the literature addressing the effect of teprotumumab treatment on objective ocular alignment measures. The purpose of our study was to address this gap.

Methods:
We performed a retrospective review of patients who were diagnosed with TED, presented with diplopia, and treated with teprotumumab in a single-center academic ophthalmology practice. The primary outcome was change in ocular alignment in primary gaze position at 6 months (completion of teprotumumab treatment). Secondary outcomes included change in ocular alignment in other gaze positions, proptosis, eyelid position, and clinical activity score (CAS) at 6 months compared with baseline. To determine what factors may predict ocular alignment response to teprotumumab, we analyzed baseline characteristics among 3 groups, divided based on whether ocular alignment was worsened, stable, or improved at 6 months.

Results:
Seventeen patients met inclusion criteria, 3 (18%) worsened, 10 (59%) were stable, and 4 (24%) improved. CAS (P = 0.02) was significantly different among the groups and was higher in those who worsened and those who improved compared with those who remained stable. Right gaze horizontal prism deviation (P = 0.01) and left gaze horizontal prism deviation (P = 0.03) were significantly different among the groups, with a greater degree of left gaze horizontal prism deviation in the worse group than the stable group (P = 0.04).

Conclusions:
Our study demonstrated that most patients remained stable after teprotumumab treatment regarding ocular alignment in primary gaze and the number of patients who improved was slightly higher than the number of patients who worsened after teprotumumab treatment. There are some baseline measures, such as CAS and right and left gaze horizontal prism deviation that can help better predict how a patient will respond to teprotumumab treatment. Our results can better inform physicians of how to counsel patients with TED when considering teprotumumab therapy.
Smoking-informed methylation and expression QTLs in human brain and colocalization with smoking-associated genetic loci
Authors: Carnes Megan Ulmer , Quach Bryan C. , Zhou Linran , Han Shizhong , Tao Ran , Mandal Meisha , Deep-Soboslay Amy , Marks Jesse A. , Page Grier P. , Maher Brion S. , Jaffe Andrew E. , Won Hyejung , Bierut Laura J. , Hyde Thomas M. , Kleinman Joel E. , Johnson Eric O. , Hancock Dana B. 
Published: September 2023

AbstractSmoking is a leading cause of preventable morbidity and mortality. Smoking is heritable, and genome-wide association studies (GWAS) of smoking behaviors have identified hundreds of significant loci. Most GWAS-identified variants are noncoding with unknown neurobiological effects. We used genome-wide genotype, DNA methylation, and RNA sequencing data in postmortem human nucleus accumbens (NAc) to identifycis-methylation/expression quantitative trait loci (meQTLs/eQTLs), investigate variant-by-cigarette smoking interactions across the genome, and overlay QTL evidence at smoking GWAS-identified loci to evaluate their regulatory potential. Active smokers (N=52) and nonsmokers (N=171) were defined based on cotinine biomarker levels and next-of-kin reporting. We simultaneously tested variant and variant-by-smoking interaction effects on methylation and expression, separately, adjusting for biological and technical covariates and using a two-stage multiple testing approach with eigenMT and Bonferroni corrections. We found >2 million significant meQTL variants (padj<0.05) corresponding to 41,695 unique CpGs. Results were largely driven by main effects; five meQTLs, mapping toNUDT12,FAM53B,RNF39, andADRA1B, showed a significant interaction with smoking. We found 57,683 significant eQTLs for 958 unique eGenes (padj<0.05) and no smoking interactions. Colocalization analyses identified loci with smoking-associated GWAS variants that overlapped meQTLs/eQTLs, suggesting that these heritable factors may influence smoking behaviors through functional effects on methylation/expression. One locus containingMUSTIN1andITIH4colocalized across all data types (GWAS + meQTL + eQTL). In this first genome-wide meQTL map in the human NAc, the enriched overlap with smoking GWAS-identified genetic loci provides evidence that gene regulation in the brain helps explain the neurobiology of smoking behaviors.
Patient-Derived Medullary Thyroid Cancer Organoids; a Model for Patient-tailored Drug and PET-Tracer Screening
Authors: Sondorp Luc H.J. , Jager Eline C. , Antunes Inês F. , Maturi Rufina , Jansen Liesbeth , Zandee Wouter T. , Brouwers Adrienne H. , Links Thera P. , Coppes Robert P. , Kruijff Schelto 
Published: September 2023

AbstractBackgroundMedullary thyroid carcinoma (MTC) is a neuroendocrine tumor derived from the parafollicular C-cells of the thyroid gland. PET imaging, with various PET tracers, is performed when distant metastatic disease is suspected. After the recognition of progressive disease on imaging, targeted therapy may be initiated to prolong survival. Mutations in the gene encoding the REarranged during Transfection (RET) tyrosine kinase play a key role in the development of MTC. It seems that tyrosine kinase inhibitors (TKIs) inhibit tumor proliferation, but it remains challenging to determine the best patient specific treatment option. Here, we aim to set up anin vitroMTC organoid model to study its potential for patient-tailored drug-screening and uptake of PET tracers.MethodsDispersed cells obtained from surgical MTC biopsies were suspended in Matrigel with defined medium allowing MTC organoid formation. To study putative MTC stem cells, the self-renewal potential of organoids was tested by dissociation to single cells and re-plating. To check MTC origin, MTC-specific gene expression and proteins were characterized by qPCR and immunofluorescent (IF) staining. To investigate cytotoxicity, MTC-organoids (MTOs) were exposed to various TKIs after which hormone (calcitonin and CEA) excretion levels were determined. Lastly, we evaluated cell-specific uptake of clinically used Positron Emission Tomography (PET) tracers.ResultsNine MTC biopsies were processed and cultured as MTOs. Eight MTO lines were used to determine organoid formation efficiency (OFE), which yielded a maximum OFE of 6.3% in passage 1 (p1), 5.9% in p2, and 9.4% in p3, indicating the presence of putative stem cells. IF staining showed expression of MTC-specific markers in both tissue and MTOs showing tissue resemblance. Tumor marker measurements in MTO medium showed MTC-specific production of calcitonin and CEA with changed concentrations after exposure to TKIs. Exposure to PET tracers showed significant uptake in the MTOs.ConclusionMTC organoids can be successfully cultured and resemble the tissue of origin in gene expression, protein expression and functionality. In addition, MTOs can take up PET tracers, and have the potential to be used as a prediction model for TKI treatment in the future.
COVID-19 Vaccine Acceptance and Hesitancy in Ghana: A Systematic Review
Authors: Akrong Godwin Banafo , Hiadzi Rosemond Akpene , Donkor Antonia Bernadette , Anafo Daniel Kwasi 
Published: September 2023

AbstractThe propensity to accept vaccines and factors that affect vaccine acceptance and hesitancy will determine the overall success of the COVID-19 vaccination program. Therefore, it is essential for countries to understand the factors that influence vaccine acceptance and hesitancy in order to prevent further future shocks, and it is necessary to have a thorough understanding of these factors. This study, as a result, aims to review selected published works in the domain of study and conduct valuable analysis to determine the most influential factors in COVID-19 vaccine acceptance and hesitancy in Ghana. The review also explored the acceptance rate of COVID-19 vaccines in Ghana. We selected published works from 2021 to April 2023 and extracted, analyzed, and summarized the findings based on the key factors that influence COVID-19 vaccine acceptance and hesitancy in Ghana, the acceptance rate in Ghana, the demographic factors that are often examined, and the study approach used to examine these factors. The study found that positive vaccination perception, safety, belief in vaccine efficacy, knowledge of COVID-19, and a good vaccine attitude influence COVID-19 vaccine acceptance in Ghana. The negative side effects of the vaccines, mistrust in the vaccine, lack of confidence in the safety of the vaccines, fear, and spiritual and religious beliefs all played significant roles in the factors influencing COVID-19 vaccine hesitancy. The demographic parameters frequently included in these studies that have a significant impact include educational attainment, gender, religious affiliation, age, and marital status.
Metabolic health tracking using Ultrahuman M1 continuous glucose monitoring platform in non- and pre-diabetic Indians: a multi-armed observational study
Authors: Chaudhry Monik , Kumar Mohit , Singhal Vatsal , Srinivasan Bhuvan 
Published: September 2023

AbstractBackgroundCGM-based tracking is expanding in non-diabetic groups to meet wellness and preventive care needs. However, data is limited on short-term outcomes for glycemic control, insulin resistance and correlation of algorithm-derived score to known glycemic metrics in controlled settings, making benchmarking difficult. This is especially true for the high-risk Indian/South Asian demographic.ObjectivesTo examine changes resulting from the Ultrahuman (UH) M1 CGM application-with concomitant FitBit tracker use in patterns of glucose variability (GV). Evaluate GV correlations with stress, sleep duration, inflammation, and activity. Examine correlations between UH metabolic score (UH-MS) and biomarkers of dysglycemia and insulin resistance.MethodsParticipants (N=53 non-diabetic, 52 pre-diabetic) wore the UH-M1 CGM and FitBit tracker for a 14-day period. HsCRP, cortisol, OGTT, HbA1c, HOMA-IR levels, and standard blood profile measurements were obtained.ResultsMean glucose levels, restricted time in range (70-110mg/dL), and GV metrics were significantly different between non- and pre-diabetics and displayed improvements with M1 use. Strong correlations of specific GV metrics with inflammation were found in pre-diabetics, with modest correlation between sleep and activity in non-diabetics. Elevated HOMA-IR, HbA1c, and OGTT were linked with J-index and high blood glucose index in pre-diabetics, and low blood glucose index in non-diabetics. UH-MS displayed a strong inverse relationship with insulin resistance and glucose dysregulation.ConclusionsThe study presents the first guidance values of glycemic indices of non- and pre-diabetic Indians and supports the notion that short-duration CGM use with algorithm scores can affect positive changes in glucose management.
Discovering chromatin dysregulation induced by protein-coding perturbations at scale
Authors: Frenkel Max , Hujoel Margaux L.A. , Morris Zachary , Raman Srivatsan 
Published: September 2023

AbstractAlthough population-scale databases have expanded to millions of protein-coding variants, insight into variant mechanisms has not kept pace. We present PROD-ATAC, a high-throughput method for discovering the effects of protein-coding variants on chromatin. A pooled library of variants is expressed in a disease-agnostic cell line, and single-cell ATAC resolves each variant’s effect on chromatin. Using PROD-ATAC, we characterized the effects of >100 oncofusions (a class of cancer-causing chimeric proteins) and controls and revealed that pioneer activity is a common feature of fusions spanning an enormous range of fusion frequencies. Further, fusion-induced dysregulation can be context-agnostic as observed mechanisms often overlapped with cancer and cell-type specific prior knowledge. We also showed that gain-of-function pioneering is common among oncofusions. This work provides a global view of fusion-induced chromatin. We uncovered convergent mechanisms among disparate oncofusions and shared modes of dysregulation across different cancers. PROD-ATAC is generalizable to any set of protein-coding variants.
Does top managers' tenure matter to management accounting system design?
Authors: Ahmed Mohamed M.M. 
Published: September 2023

PurposeThis study aims to investigate the relationship between top manager tenure and the sophistication level of management accounting system (MAS) in extant literature.Design/methodology/approachCumulating evidence from 31 studies (N = 12,739), this study meta-analytically examines the central question of whether top managers' tenure is significantly associated with MAS sophistication after correcting individual studies for statistical artifacts. The study also assesses the strength of this association bniy exploring the influence of several moderating factors.FindingsThe findings show that long-tenured top managers are not significantly related to MAS sophistication. However, the moderator analtgcqyses indicate that the relationship between top manager tenure and MAS sophistication is moderated by tenure measurement type, firm sector and size. The study provides evidence for the significant moderation of tenure measurement type (i.e. position tenure). The results also argue that top manager tenure matters for MAS sophistication in small- and medium-sized enterprises (SMEs) and firms in the private sector.Originality/valueThe meta-analysis summarizes existing studies quantitatively to expand prior narrative reviews by providing definitive evidence of the overall effect of top manager tenure on MAS sophistication.