bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current approaches to management of vocal fold scar
Authors: Allen Jacqui 
Published: October 2021

Purpose of review
Vocal fold (VF) fibrosis remains an insoluble problem in most cases, with a severe impact on vocal quality and effort. This review examines current investigations and research strands that explore the understanding of VF wound healing and applied treatments for the management of VF scar.

Recent findings
Recent work focused on VF fibrosis has examined wound healing in the glottis, fibrosis-modifying medication, and tissue engineering approaches that span cytokine and growth factor therapy, scaffold and cell delivery platforms, seeded scaffolds, conditioned media and stem cell therapy. Many show promise and may deliver improvements in the wound bed favouring less fibrogenic healing patterns, ultimately with the goal of preserving or restoring VF vibration. Further collaborative research is required that examines combined approaches, long term outcomes, better three-dimensional modelling of cell-cell interactions and delivery modalities for molecular therapies.

Summary
VF fibrosis research continues to expand and explore a variety of mechanistic pathways in order to understand VF healing and identify novel and complementary targets for manipulation. Many different approaches show promise and may also offer synergistic benefits. Research continues to strive for healing that more closely resembles true VF architecture and function.
Pyruvate and Glutamine Define the Effects of Cholecystokinin and Ethanol on Mitochondrial Oxidation, Necrosis, and Morphology of Rat Pancreatic Acini
Authors: Manko Bohdan O. , Bilonoha Olha O. , Voloshyn Dariia M. , Zub Anastasiia M. , Ivasechko Iryna I. , Manko Volodymyr V. 
Published: October 2021

Objectives
The objective of this study was to test whether pyruvate and glutamine affect the ethanol and cholecystokinin (CCK) effects on the mitochondrial function, viability, and morphology of rat pancreatic acini.

Methods
Respiration was measured with Clark oxygen electrode. Mitochondrial membrane potential, reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H), cell morphology, and viability were studied with fluorescence microscopy.

Results
In vitro, CCK (0.1 nM) caused pyruvate-dependent stimulation of basal and uncoupled respiration, and the effects were abolished by ethanol (20 mM). The combination of ethanol with CCK (2 hours) caused necrosis of approximately 40% acinar cells in medium with glucose, but not with pyruvate and/or glutamine. Cholecystokinin (10 nM) or ethanol with 0.1 nM CCK caused plasma membrane blebbing not related to apoptosis only when both glutamine and pyruvate were present. Glutamine, but not pyruvate, decreased NAD(P)H level and prevented the effects of ethanol with CCK on mitochondrial membrane potential and NAD(P)H, but, in combination with CCK and ethanol, decreased the uncoupled respiration. In vivo, the combination of ethanol (4 g/kg) and CCK (20 pmol/kg) suppressed basal and uncoupled respiration and caused acinar cell blebbing, but not necrosis.

Conclusions
The lack of sufficient substrate supply in vitro makes pancreatic acinar cells susceptible to necrosis caused by ethanol and CCK in clinically relevant concentrations.
Exome Sequencing of Pancreatic Acinar Carcinoma Identified Distinctive Mutation Patterns
Authors: Liu Yuanhang , Raimondo Massimo , Wallace Michael B. , Mody Kabir , Stauffer John A. , Zhang Lizhi , Ji Baoan , Bi Yan 
Published: October 2021

Objectives
Pancreatic acinar cell carcinoma (ACC) is a rare pancreatic cancer. The advancement of treatment is hampered because of the limited knowledge of its molecular mechanism.

Methods
Whole-exome sequencing was performed on DNA extracted from 11 pure ACC surgical samples. Potential germline variants were removed on the basis of polymorphic databases, alternative allele frequency, coverage depth, and Catalogue of Somatic Mutations in Cancer (COSMIC) annotations after variant calling procedure. Mutation profiles and signatures were assessed through the Mutational Patterns package.

Results
A median of 34 somatic mutations were detected (range, 19–60). Three novel recurrent small deletions were identified. Common pancreatic ductal adenocarcinoma mutations or neuroendocrine tumor mutants were not found. FAT atypical cadherin 4, mucin 5B, titin, and zinc finger homeobox 3 were consistently mutated across 4 independent ACC studies. A high contribution of COSMIC mutational signature 1 was seen in ACC, indicating deamination of 5-methylcytosine. The majority of the patients had COSMIC signatures 6, 15, or 20, relating to defective DNA mismatch repair. Six patients showed COSMIC mutational signature 10 because of the altered activity of DNA polymerase epsilon.

Conclusions
Distinct mutational signatures pathways were found in ACC and targeting them may improve clinical outcome.
Rectally Administered Low-Dose Diclofenac Has No Effect on Preventing Post–Endoscopic Retrograde Cholangiopancreatography Pancreatitis
Authors: Takaori Ayaka , Ikeura Tsukasa , Hori Yuichi , Ito Takashi , Nakamaru Koh , Masuda Masataka , Mitsuyama Toshiyuki , Miyoshi Hideaki , Shimatani Masaaki , Takaoka Makoto , Okazaki Kazuichi , Naganuma Makoto 
Published: October 2021

Objectives
We evaluated the preventive effect of low-dose diclofenac (25–50 mg) on post–endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) by propensity score matching analysis.

Methods
We retrospectively analyzed the data of 515 patients who underwent ERCP for the first time with or without the rectal administration of low-dose diclofenac before the procedure. For the purpose of minimization of the intrinsic selection bias, we compared the incidence rate of PEP between the diclofenac and control group after propensity score matching.

Results
Post-ERCP pancreatitis developed in 15 patients (2.9%). There was no significant difference in the incidence of PEP between the diclofenac (2.4%) and control group (3.3%) (P = 0.608). One hundred ninety matched pairs were generated by propensity score matching and analyzed; however, the incidence rate of PEP was the same in both groups (2.1%, P = 1.000). In the subgroup analysis using data of patients with high-risk factors for developing PEP, the incidence rate of PEP was comparable between the diclofenac (3.8%) and control groups (4.0%) (P = 0.917).

Conclusions
In our propensity score analysis, rectal administration of low-dose diclofenac was not shown to be useful in preventing PEP.
Impact of Renal Function on S-1 + Radiotherapy for Locally Advanced Pancreatic Cancer
Authors: Kobayashi Satoshi , Ueno Makoto , Ogawa Gakuto , Fukutomi Akira , Ikeda Masafumi , Okusaka Takuji , Sato Tosiya , Ito Yoshinori , Kadota Tomohiro , Ioka Tatsuya , Sugimori Kazuya , Sata Naohiro , Nakamori Shoji , Shimizu Kyoko , Mizuno Nobumasa , Ishii Hiroshi , Furuse Junji 
Published: October 2021

Objectives
S-1 monotherapy with concurrent radiotherapy (RT) is a standard of care for patients with locally advanced pancreatic cancer (LAPC). Although renal dysfunction increases S-1 monotherapy toxicity, its effect in S-1 with concurrent RT remains unknown. We evaluated the effect of renal function on the safety of S-1 with RT for LAPC.

Methods
We performed an integrated exploratory post hoc analysis of data from 2 prospective studies (JCOG1106 and LAPC-S1RT), where patients with LAPC received RT (50.4 Gy/28 fraction for 5.5 weeks) and concurrent S-1 (40 mg/m2 per dose, twice daily on the day of irradiation). We split the patients into high creatinine clearance (CCr; ≥80 mL/min) and low CCr (<80 mL/min) groups and compared the findings to determine treatment safety.

Results
The high and low CCr groups showed a median of 97.5 (range, 80.0–194.6) and 64.4 (range, 50.0–78.3) mL/min, respectively. The low CCr group presented more adverse reactions (ARs) of grade 3 or higher and gastrointestinal ARs of grade 2 or higher than the high CCr group (30.8% vs 15.8% and 51.9% vs 36.8%).

Conclusions
The incidence of ARs associated with concurrent S-1 and RT increases in patients with low CCr; therefore, ARs should be duly considered in such patients.
Factors Associated With Physical Therapy Engagement During the Period of Posttraumatic Amnesia
Authors: Spiteri Courtney , Williams Gavin , Kahn Michelle , Ponsford Jennie , McKay Adam 
Published: October 2021

Background and Purpose:
Physical therapy is important in the management of traumatic brain injury (TBI) and associated multitrauma. Providing therapy during the posttraumatic amnesia (PTA) phase is challenging, given that hallmark features including confusion, amnesia, agitation, and fatigue may impede the person's ability to engage in and benefit from rehabilitation. To date, there is little empirical evidence to guide the provision of therapy during PTA. This observational study aimed to explore the frequency, duration, location, and engagement of physical therapy provision during PTA and the impact of cognition, agitation, and fatigue.

Summary of Key Points:
The majority of patients were found to meaningfully engage and participate in physical therapy for the majority of sessions. Only a small proportion were unable to participate in physical therapy. Patient refusal and fatigue were identified as the most prominent barriers to rehabilitation. Despite fatigue and agitation reaching clinical levels, therapy could still successfully proceed on most occasions.

Recommendations for Clinical Practice:
Physical therapy is feasible during the acute recovery stages after TBI. Current results support the notion that therapy should commence early to minimize secondary complications and promote the recovery of mobility. A patient-centered therapeutic model that tailors the therapeutic approach to meet the individual's current physical and fluctuating cognitive capabilities may be most suited for this population. Clinicians working with people after TBI need experience in understanding and managing the cognitive limitations and associated symptoms of PTA to optimize the provision of therapy. These findings could inform guidelines for the management of patients in PTA.

Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A368).
Association Between Posttraumatic Stress Disorder and Epigenetic Age Acceleration in a Sample of Twins
Authors: Wang Zeyuan , Hui Qin , Goldberg Jack , Smith Nicholas , Kaseer Belal , Murrah Nancy , Levantsevych Oleksiy M. , Shallenberger Lucy , Diggers Emily , Bremner J. Douglas , Vaccarino Viola , Sun Yan V. 
Published: October 2021

ABSTRACT

Objective
Posttraumatic stress disorder (PTSD) has been related to accelerated biological aging processes, but objective evidence for this association is limited. DNA methylation (DNAm) age acceleration is a novel measure of biological aging that may help clarify if PTSD is related to biological aging processes. We aim to examine whether PTSD is associated with biological aging using a comprehensive set of DNAm age acceleration markers and to what extent the unshared environment contributes to the association.

Methods
Using a cross-sectional co-twin control study design, we investigated the association of the clinical diagnosis and symptom severity of PTSD with six measurements of DNAm age acceleration based on epigenome-wide data derived from peripheral blood lymphocytes of 296 male twins from the Vietnam Era Twin Registry.

Results
Twins with current PTSD had significantly advanced DNAm age acceleration compared with twins without PTSD for five of six measures of DNAm age acceleration. Across almost all measures of DNAm age acceleration, twins with current PTSD were “epigenetically older” than their twin brothers without PTSD: estimated differences ranged between 1.6 (95% confidence interval = 0.0–3.1) and 2.7 (95% confidence interval = 0.5–4.8) biological age year-equivalents. A higher Clinician-Administered PTSD Scale score was also associated with a higher within-pair DNAm age acceleration. Results remained consistent after adjustment for behavioral and cardiovascular risk factors.

Conclusions
PTSD is associated with epigenetic age acceleration, primarily through unshared environmental mechanisms as opposed to genetic or familial factors. These results suggest that PTSD is related to systemic processes relevant to biological aging.
A Comparison of Oral Health Outcomes of Self-Reported and Agency-Notified Child Maltreatment in a Population-Based Birth Cohort at 30-Year-Old Follow-Up
Authors: Kisely Steve , Strathearn Lane , Najman Jake Moses 
Published: October 2021

ABSTRACT

Objective
Information on the oral health outcomes of childhood maltreatment in adulthood is limited and reliant on retrospective questionnaires that are subject to recall bias. There are no data from prospective studies using maltreatment reports to statutory agencies. We therefore assessed the effect on dental outcomes and oral health care at 30-year follow-up using both prospective agency notifications and retrospective self-reports of child maltreatment in the same birth cohort.

Methods
There were 2456 adults with data on dental outcomes and oral health care at follow-up. Information on self-reported abuse was collected using the Child Trauma Questionnaire and linked to child maltreatment notifications to statutory agencies.

Results
The prevalence of self- and agency-reported maltreatment was 599 (24.4%) and 142 (5.8%), respectively. At follow-up, 850 participants (34.6%) had undergone a dental extraction for infection or decay, and 810 had experienced significant dental pain over their lifetime. One-third had not visited a dental clinic in the previous 2 years, and 40% failed to brush their teeth at least twice daily. On adjusted analyses, both self- and agency-reported maltreatment showed significant associations with dental extraction (odds ratio = 1.47 [95% confidence interval = 1.21–1.80] and odds ratio = 1.44 [95% confidence interval = 1.01–2.06], respectively). There were similar results for brushing frequency, whereas self-reported maltreatment was associated with dental pain. However, associations were weaker for dental clinic visits and some child maltreatment subtypes.

Conclusions
Child maltreatment is associated with adverse oral health consequences in adulthood and is thus a dental and wider public health issue.
Interferon Gamma Release Assay and Tuberculin Skin Test Performance in Pregnant Women Living With and Without HIV
Authors: Kaplan Samantha R. , Escudero Jaclyn N. , Mecha Jerphason , Richardson Barbra A. , Maleche-Obimbo Elizabeth , Matemo Daniel , Kinuthia John , John-Stewart Grace C. , LaCourse Sylvia M. 
Published: October 2021

Background:
HIV and pregnancy may affect latent TB infection (LTBI) diagnostics. Tuberculin skin test (TST) and newer generation QuantiFERON-TB Gold Plus (QFT-Plus) evaluations in pregnant women living with HIV (WLHIV) and without HIV are lacking.

Methods:
In this cross-sectional study, pregnant women underwent TST and QFT-Plus testing during antenatal care in Kenya. We estimated LTBI prevalence and TST and QFT-Plus performances. Diagnostic agreement was assessed with kappa statistic, participant characteristics associated with LTBI and HIV were assessed with generalized linear models, and QFT-Plus quantitative responses were assessed with Mann–Whitney U test.

Results:
We enrolled 400 pregnant women (200 WLHIV/200 HIV-negative women) at median 28 weeks gestation (interquartile range 24–30). Among WLHIV (all on antiretroviral therapy), the median CD4 count was 464 cells/mm3 (interquartile range 325–654); 62.5% (125) had received isoniazid preventive therapy. LTBI prevalence was 35.8% and similar among WLHIV and HIV-negative women. QFT-Plus testing identified 3-fold more women with LTBI when compared with TST (32% vs. 12%, P < 0.0001). QFT-Plus positivity prevalence was similar regardless of HIV status, although TB-specific antigen responses were lower in WLHIV than in HIV-negative women with LTBI (median QFT-TB1 1.05 vs. 2.65 IU/mL, P = 0.035; QFT-TB2 1.26 vs. 2.56 IU/mL, P = 0.027). TST positivity was more frequent among WLHIV than among HIV-negative women (18.5% vs 4.6%; P < 0.0001).

Conclusions:
QFT-Plus assay had higher diagnostic yield than TST for LTBI in WLHIV and HIV-negative women despite lower TB-specific antigen responses in WLHIV. Higher TST positivity was observed in WLHIV. LTBI diagnostic performance in the context of pregnancy and HIV has implications for clinical use and prevention studies, which rely on these diagnostics for TB infection entry criteria or outcomes.
Applications of Mechanical Arm in the Virtual Touch Tissue Imaging Quantification and the Differential Diagnosis of Breast Tumors
Authors: Li Ling , Lv Guorong , Shen Haolin , Liao Liping , Zhong Rong , Zheng Chunnuan , Yang Shuping 
Published: October 2021

Abstract
To assess the diagnostic performance of quantitative parameters for virtual touch tissue imaging quantification by the mechanical arm probe, 128 women with 152 breast lesions (90 benign and 62 malignant) were included and maximum elasticity (V
max), median elasticity (V
mean), maximum elasticity minus minimum (V
max-min), and minimum elasticity (V
min) were measured. Intercorrelation coefficients and Bland-Altman plots were used to compare the repeatability and consistency of handheld probe and mechanical arm measurements. Receiver operating characteristic curve was used to evaluate the diagnostic efficiency. The results showed that intercorrelation coefficients were 0.694 to 0.951 by the mechanical arm and 95% limits of agreement were wider than handheld probe. Using 4.36 m/s as cutoff value for V
max by the mechanical arm, we achieved sensitivity (88.7%) and specificity (90.0%). We concluded that the mechanical arm can reduce the influence of different scanning pressures on the elastic modulus of breast tissue.
Low Titer Group O Whole Blood In Injured Children Requiring Massive Transfusion
Authors: Gaines Barbara A. , Yazer Mark H. , Triulzi Darrell J. , Sperry Jason L. , Neal Matthew D. , Billiar Timothy R. , Leeper Christine M. 
Published: October 2021

Objective:
The aim of this study was to assess the survival impact of low-titer group O whole blood (LTOWB) in injured pediatric patients who require massive transfusion.

Summary Background Data:
Limited data are available regarding the effectiveness of LTOWB in pediatric trauma.

Methods:
A prospective observational study of children requiring massive transfusion after injury at UPMC Children’s Hospital of Pittsburgh, an urban academic pediatric Level 1 trauma center. Injured children ages 1 to 17 years who received a total of >40 mL/kg of LTOWB and/or conventional components over the 24 hours after admission were included. Patient characteristics, blood product utilization and clinical outcomes were analyzed using Kaplan-Meier survival curves, log rank tests and Cox proportional hazards regression analyses. The primary outcome was 28-day survival.

Results:
Of patients analyzed, 27 of 80 (33%) received LTOWB as part of their hemostatic resuscitation. The LTOWB group was comparable to the component therapy group on baseline demographic and physiologic parameters except older age, higher body weight, and lower red blood cell and plasma transfusion volumes. After adjusting for age, total blood product volume transfused in 24 hours, admission base deficit, international normalized ratio (INR), and injury severity score (ISS), children who received LTOWB as part of their resuscitation had significantly improved survival at both 72 hours and 28 days post-trauma [adjusted odds ratio (AOR) 0.23, P = 0.009 and AOR 0.41, P = 0.02, respectively]; 6-hour survival was not statistically significant (AOR = 0.51, P = 0.30). Survivors at 28 days in the LTOWB group had reduced hospital LOS, ICU LOS, and ventilator days compared to the CT group.

Conclusion:
Administration of LTOWB during the hemostatic resuscitation of injured children requiring massive transfusion was independently associated with improved 72-hour and 28-day survival.
Surgical stabilization of severe chest wall injury following cardiopulmonary resuscitation
Authors: DeVoe William B. , Abourezk Matthew , Goslin Brent J. , Saraswat Nirvana , Kiel Brandon , Bach John A. , Suh Kwang I. , Eriksson Evert A. 
Published: October 2021

BACKGROUND
Cardiopulmonary resuscitation (CPR) contributes to significant chest wall injury similar to blunt trauma. With benefits realized for surgical stabilization of rib fractures (SSRFs) for flail injuries and severely displaced fractures following trauma, SSRF for chest wall injury following CPR could be advantageous, provided good functional and neurologic outlook. Experience is limited. We present a review of patients treated with SSRF at our institution following CPR.

METHODS
A retrospective analysis of patients undergoing SSRF following CPR was performed between 2019 and 2020. Perioperative inpatient data were collected with outpatient follow-up as able.

RESULTS
Five patients underwent SSRF over the course of the 2-year interval. All patients required invasive ventilation preoperatively or had impending respiratory. Mean age was 59 ± 12 years, with all patients being male. Inciting events for cardiac arrest included respiratory, ventricular tachycardia, ventricular fibrillation, pulseless electrical activity, and anaphylaxis. Time to operation was 6.6 ± 3 days. Four patients demonstrated anterior flail injury pattern with or without sternal fracture, with one patient having multiple severely displaced fractures. Surgical stabilization of rib fracture was performed appropriately to restore chest wall stability. Mean intensive care unit length of stay was 9.8 ± 6.4 days and overall hospital length of stay 24.6 ± 13.2 days. Median postoperative ventilation was 2 days (range, 1–15 days) with two patients developing pneumonia and one requiring tracheostomy. There were no mortalities at 30 days. One patient expired in hospice after a prolonged hospitalization. Disposition destination was variable. No hardware complications were noted on outpatient follow-up, and all surviving patients were home.

CONCLUSION
Chest wall injuries are incurred frequently following CPR. Surgical stabilization of these injuries can be considered to promote ventilator liberation and rehabilitation. Careful patient selection is paramount, with surgery offered to those with reversible causes of arrest and good functional and neurologic outcome. Experience is early, with further investigation needed.

LEVEL OF EVIDENCE
Therapeutic, Level V.