bluuebunny/crossref_metadata_2025 huggingface dataset:
A preliminary study of radioulnar wrist compression in improving patient-reported outcomes of carpal tunnel syndrome
Authors: Li Zong-Ming , Grandy Emily L. , Jenkins Lenicia , Norman Carli , Bena James , Hou Juliet , Evans Peter J. , Seitz William H. , Kwoh C. Kent
Published: November 2022

Previous studies have shown radioulnar wrist compression augments carpal arch space. This study investigated the effects of radioulnar wrist compression on patient-reported outcomes associated with carpal tunnel syndrome. Subjects underwent thrice-daily (15 min each time 45 min daily) wrist compression over 4 weeks with an additional four weeks of follow-up without treatment. Primary outcomes included Boston Carpal Tunnel Questionnaire symptom and functional severity scales (SSS and FSS) and symptoms of numbness/tingling based on Visual Analog Scales. Our results showed that radioulnar wrist compression improved SSS by 0.55 points after 2 weeks (p < 0.001) and 0.51 points at 4 weeks (p < 0.006) compared to the baseline scale. At the four-week follow-up, SSS remined improved at 0.47 points (p < 0.05). Symptoms of numbness/tingling improved at two and 4 weeks, as well as the follow-up (p < 0.05). Hand motor impairment such as weakness had a lower frequency across carpal tunnel syndrome sufferers and does not significantly improve (p > 0.05). Radioulnar wrist compression might be an effective alternative treatment in improving sensory related symptoms in patients with mild to moderate carpal tunnel syndrome.
Neoadjuvant versus adjuvant chemotherapy in upper tract urothelial carcinoma: A nationwide cohort study
Authors: Tae Jong Hyun , Ha Moon Soo , Chi Byung Hoon , Chang In Ho , Kim Tae-Hyoung , Myung Soon Chul , Nguyen Tuan Thanh , Kim Myoungsuk , Lee Kyung-Eun , Kim Yuwon , Woo Hyun-ki , Kyoung Dae-Sung , Kim Hasung , Choi Se Young
Published: November 2022

Purpose

This study aimed to evaluate the trend of adjuvant chemotherapy (AC) and neoadjuvant chemotherapy (NAC) in patients who underwent radical nephroureterectomy with bladder cuff excision (NUx) for upper tract urothelial carcinoma (UTUC) to compare the perioperative outcomes and overall survival (OS) between AC and NAC using nationwide population-based data.

Materials and methods

We collected data on patients diagnosed with UTUC and treated with NUx between 2004 and 2016 using the National Health Insurance Service database, and evaluated the overall treatment trends. The AC and NAC groups were propensity score-matched. Cox proportional hazard and Kaplan-Meier analyses were used to assess survival.

Results

Of the 8,705 enrolled patients, 6,627 underwent NUx only, 94 underwent NAC, and 1,984 underwent AC. The rate of NUx without perioperative chemotherapy increased from 70.8 to 78.2% (R2 = 0.632; p < 0.001). The rates of dialysis (p = 0.398), TUR-BT (p = 1.000), and radiotherapy (p = 0.497) after NUx were similar. In the Kaplan-Meier curve, the NAC and AC groups showed no significant difference (p = 0.480). In multivariate analysis, treatment with AC or NAC was not associated with OS (hazard ratio 0.83, 95% confidence interval 0.49–1.40, p = 0.477).

Conclusion

The use of NUx without perioperative chemotherapy has tended to increase in South Korea. Dialysis, TUR-BT, and radiotherapy rates after NUx were similar between the NAC and AC groups. There was no significant difference in OS between the NAC and AC groups. Proper perioperative chemotherapy according to patient and tumor conditions should be determined by obtaining more evidence of UTUC.
Comparison of full-dose gemcitabine/cisplatin, dose-reduced gemcitabine/cisplatin, and gemcitabine/carboplatin in real-world patients with advanced urothelial carcinoma
Authors: Sugimoto Kazuma , Taguchi Satoru , Kishitani Kenjiro , Kawai Taketo , Masuda Kazuki , Nakamura Yu , Kinjo Manami , Tambo Mitsuhiro , Miyakawa Jimpei , Akiyama Yoshiyuki , Yamada Yuta , Sato Yusuke , Yamada Daisuke , Nakagawa Tohru , Fukuhara Hiroshi , Kume Haruki
Published: November 2022

Background

While gemcitabine/cisplatin (GC) is the gold standard regimen for patients with advanced urothelial carcinoma (aUC), either dose-reduced GC or gemcitabine/carboplatin (GCa) is an alternative option for “cisplatin-unfit” patients. However, few studies have compared outcomes with these commonly used regimens in the real-world setting.

Methods

We retrospectively reviewed patients with aUC who received full-dose GC, dose-reduced GC, or GCa as first-line salvage chemotherapy at two university hospitals between 2016 and 2020. Progression-free survival, cancer-specific survival, and overall survival, as well as best overall response and adverse event profiles, were compared among these three regimens.

Results

Of 105 patients, 41, 27, and 37 patients received full-dose GC, dose-reduced GC, and GCa, respectively. Significant differences were noted in the patients’ baseline age, primary site, and renal function among the three regimens. Sixty-nine (65.7%) patients died during a median follow-up period of 14 months. There was no significant difference among the three regimens for all survival outcomes and best overall response. However, the complete response rate of dose-reduced GC (2/27, 7.4%) appeared inferior to that of full-dose GC (9/41, 22.0%) or GCa (6/37, 16.2%). Regarding adverse event profiles, no significant difference was observed among the three regimens, except for significantly fewer cases with elevated alanine aminotransferase in the GCa group compared with the other groups.

Conclusions

This study compared the oncological and toxicological outcomes of full-dose GC, dose-reduced GC, and GCa in real-world patients with aUC. Unlike in the clinical trial setting, there were almost no significant differences among the three regimens.
Depression was associated with younger age, female sex, obesity, smoking, and physical inactivity, in 1027 patients with newly diagnosed type 2 diabetes: a Swedish multicentre cross-sectional study
Authors: Melin Eva O. , Wanby Pär , Neumark Thomas , Holmberg Sara , Neumark Ann-Sofi Nilsson , Johansson Karin , Landin-Olsson Mona , Thulesius Hans , Hillman Magnus , Thunander Maria
Published: November 2022

Background

Depression is a risk factor for type 2 diabetes (T2D) and cardiovascular disease (CVD). The aims were to explore the prevalence of depression, anxiety, antidepressant use, obesity, Hemoglobin A1c > 64 mmol/mol, life-style factors, pre-existing CVD, in patients with newly diagnosed T2D; to explore associations with depression; and to compare with Swedish general population data.

Methods

Multicentre, cross-sectional study. Inclusion criteria: adults with serologically verified newly diagnosed T2D. Included variables: age, sex, current depression and anxiety (Hospital Anxiety and Depression Scale), previous depression, antidepressant use, obesity (BMI ≥ 30 and ≥ 40 kg/m2), Hemoglobin A1c, pre-existing CVD. Logistic regression analyses were performed.

Results

In 1027 T2D patients, aged 18–94 years, depression was associated with age (per year) (inversely) (odds ratio (OR) 0.97), anxiety (OR 12.2), previous depression (OR 7.1), antidepressant use (OR 4.2), BMI ≥ 30 kg/m2 (OR 1.7), BMI ≥ 40 kg/m2 (OR 2.3), smoking (OR 1.9), physical inactivity (OR 1.8), and women (OR 1.6) (all p ≤ 0.013).

Younger women (n = 113), ≤ 59 years, compared to younger men (n = 217) had higher prevalence of current depression (31% vs 12%), previous depression (43 vs 19%), anxiety (42% vs 25%), antidepressant use (37% vs 12%), BMI ≥ 30 kg/m2 (73% vs 60%) and BMI ≥ 40 kg/m2) (18% vs 9%), and smoking (26% vs 16%) (all p ≤ 0.029).

Older women (n = 297), ≥ 60 years, compared to older men (n = 400) had higher prevalence of previous depression (45% vs 12%), anxiety (18% vs 10%), antidepressant use (20% vs 8%), BMI ≥ 30 kg/m2 (55% vs 47%), BMI ≥ 40 kg/m2 (7% vs 3%) (all p ≤ 0.048), but not of current depression (both 9%).

Compared to the Swedish general population (depression (women 11.2%, men 12.3%) and antidepressant use (women 9.8%, men 5.3%)), the younger women had higher prevalence of current depression, and all patients had higher prevalence of antidepressant use.

Conclusions

In patients with newly diagnosed T2D, the younger women had the highest prevalence of depression, anxiety, and obesity. The prevalence of depression in young women and antidepressant use in all patients were higher than in the Swedish general population. Three risk factors for CVD, obesity, smoking, and physical inactivity, were associated with depression.
Oral manifestations associated with inflammatory bowel disease and early endoscopic findings in patients with spondyloarthritis
Authors: Alvarado-Julio Andrés , Chumacero-Palma Katherin , Buenahora María Rosa , Parra-Izquierdo Viviana , Monsalve Mónica , Torres Ana María , Chila-Moreno Lorena , Flórez-Sarmiento Cristian , Ramos-Casallas Alejandro , De Avila Juliette , Bello-Gualtero Juan Manuel , Jaimes Diego , Beltrán-Ostos Adriana , Chalem-Choueka Philippe , Pacheco-Tena César , Bautista-Molano Wilson , Romero-Sánchez Consuelo
Published: November 2022

Background and aims

Spondyloarthritis (SpA) is a group of autoinflammatory disorders, of which the primary extra-articular manifestation is inflammatory bowel disease (IBD). The oral cavity being a part of gastrointestinal tract, is significantly compromised in IBD, and in many cases, it is the first site of clinical manifestations of IBD. This study aimed to identify changes in the oral mucosa associated with the onset of IBD and their association with endoscopic/histological findings.

Materials and methods

The study assessed 80 patients with SpA and 52 healthy controls. Oral, rheumatological, and gastroenterological assessments were performed. The ileocolonoscopy was performed via digital magnification chromoendoscopy. The statistical analysis consisted of Chi-square, Fisher's exact, and multiple correspondence discriminant analysis tests.

Results

From the disease cohort, 63.0% patients showed oral lesions (p = 0.050). These manifestations ranged from gingivitis (55.0%, p = 0.001), aphthous stomatitis (3.8%, p = 0.091), angular cheilitis (2.6%, p = 0.200), and perioral erythema with scaling (1.3%, p = 0.300). All patients who presented with alterations in colonic mucosa also had oral lesions associated with IBD (p = 0.039), specifically gingivitis/aphthous stomatitis (p = 0.029).

Conclusion

The patients with SpA without IBD present significant oral signs and symptoms. Gingivitis seems to be the most relevant because of its associations with early endoscopic and histological findings.

Clinical relevance

An integral approach to the diagnostic tests that includes evaluations of oral, rheumatological and gastroenterological tissues may favor timely attention and improve patients’ quality of life.
Machine learning methods to predict 30-day hospital readmission outcome among US adults with pneumonia: analysis of the national readmission database
Authors: Huang Yinan , Talwar Ashna , Lin Ying , Aparasu Rajender R.
Published: November 2022

Background

Hospital readmissions for pneumonia are a growing concern in the US, with significant consequences for costs and quality of care. This study developed the rule-based model and other machine learning (ML) models to predict 30-day readmission risk in patients with pneumonia and compared model performance.

Methods

This population-based study involved patients aged ≥ 18 years hospitalized with pneumonia from January 1, 2016, through November 30, 2016, using the Healthcare Cost and Utilization Project-National Readmission Database (HCUP-NRD). Rule-based algorithms and other ML algorithms, specifically decision trees, random forest, extreme gradient descent boosting (XGBoost), and Least Absolute Shrinkage and Selection Operator (LASSO), were used to model all-cause readmissions 30 days post-discharge from index pneumonia hospitalization. A total of 61 clinically relevant variables were included for ML model development. Models were trained on randomly partitioned 50% of the data and evaluated using the remaining dataset. Model hyperparameters were tuned using the ten-fold cross-validation on the resampled training dataset. The area under the receiver operating curves (AUROC) and area under precision-recall curves (AUPRC) were calculated for the testing set to evaluate the model performance.

Results

Of the 372,293 patients with an index hospital hospitalization for pneumonia, 48,280 (12.97%) were readmitted within 30 days. Judged by AUROC in the testing data, rule-based model (0.6591) significantly outperformed decision tree (0.5783, p value < 0.001), random forest (0.6509, p value < 0.01) and LASSO (0.6087, p value < 0.001), but was less superior than XGBoost (0.6606, p value = 0.015). The AUPRC of the rule-based model in the testing data (0.2146) was higher than the decision tree (0.1560), random forest (0.2052), and LASSO (0.2042), but was similar to XGBoost (0.2147). The top risk-predictive rules captured by the rule-based algorithm were comorbidities, illness severity, disposition locations, payer type, age, and length of stay. These predictive risk factors were also identified by other ML models with high variable importance.

Conclusion

The performance of machine learning models for predicting readmission in pneumonia patients varied. The XGboost was better than the rule-based model based on the AUROC. However, important risk factors for predicting readmission remained consistent across ML models.
A multicriteria decision analysis (MCDA) tool to purchase implantable medical devices in Egypt
Authors: Elezbawy Baher , Fasseeh Ahmad Nader , Németh Bertalan , Gamal Mary , Eldebeiky Mariam , Refaat Remonda , Taha Amr , Rabiea Shimaa , Abdallah Marwa , Ramadan Soha , Noaman Hasnaa , Eldin Amany Bahaa , Mostafa Hossam , Nouh Sara , Zaki Asmaa , Abdelrahman Mohamed , Abaza Sherif , Kalò Zoltàn
Published: November 2022

Background

With the availability of several similar medical devices performing the same function, choosing one for reimbursement is not easy, especially if purchased for a large number of patients. The objective of this project was to create a multicriteria decision analysis (MCDA) tool, that captures and compares all implantable medical devices’ attributes, to provide an objective method for choosing among the available options in Egypt.

Method

We conducted a systematic review and expert interviews, to identify the relevant criteria for inclusion in the tool. Subsequently, a workshop was conducted, that involved experts in procuring and tendering medical devices. Experts chose the criteria, ranked them, assigned weights and scoring functions for each criterion, and then created the draft tool. A pilot phase followed; then, another workshop was conducted to fine-tune the tool. We readjusted the tool based on experts’ experience with the draft tool.

Results

The final tool included eight criteria, arranged according to their weightage: technical characteristics (29.4%), country of origin (19.5%), use in reference countries (14.9%), supply reliability (11.7%), previous use in tenders (9.0%), instant replacement within product variety (6.9%), pharmacovigilance (4.6%), and refund or replacement (4.0%). Each medical device was assessed on these eight criteria to achieve a final score, that was compared to the alternative devices’ scores. Price is not included in the MCDA tool, but it will be added in the financial evaluation phase.

Conclusion

Decisionmakers could use the MCDA tool, to make evidence-based and objective decisions for purchasing implantable devices, in the Egyptian public sector. Post price evaluation, the product with the best value will be chosen for reimbursement.

Highlights

We created an MCDA tool to help decision makers choose between alternative implantable medical devices in Egypt.

The MCDA tool includes eight criteria, where price is evaluated as a separate step.

“Technical characteristics” and “country of origin” criteria carried the highest weights, thus representing approximately 50% of the decision.
Optimized dose selective HDAC inhibitor tucidinostat overcomes anti-PD-L1 antibody resistance in experimental solid tumors
Authors: Zhang Pei , Du Yang , Bai Hua , Wang Zhijie , Duan Jianchun , Wang Xin , Zhong Jia , Wan Rui , Xu Jiachen , He Xiran , Wang Di , Fei Kailun , Yu Ruofei , Tian Jie , Wang Jie
Published: November 2022

Background

Although immune checkpoint inhibitors (ICIs) have influenced the treatment paradigm for multiple solid tumors, increasing evidence suggests that primary and adaptive resistance may limit the long-term efficacy of ICIs. New therapeutic strategies with other drug combinations are hence warranted to enhance the antitumor efficacy of ICIs. As a novel tumor suppressor, histone deacetylase (HDAC) inhibitor tucidinostat has been successfully confirmed to act against hematological malignancies. However, the underlying mechanisms of action for tucidinostat and whether it can manipulate the tumor microenvironment (TME) in solid tumors remain unclear.

Methods

Three murine tumor models (4T1, LLC, and CT26) were developed to define the significant role of different doses of tucidinostat in TME. The immunotherapeutic effect of tucidinostat combined with anti-programmed cell death ligand 1 antibody (aPD-L1) was demonstrated. Furthermore, the effect of tucidinostat on phenotypic characteristics of peripheral blood mononuclear cells (PBMCs) from lung cancer patients was investigated.

Results

With an optimized dose, tucidinostat could alter TME and promote the migration and infiltration of CD8+ T cells into tumors, partially by increasing the activity of C-C motif chemokine ligand 5 (CCL5) via NF-κB signaling. Moreover, tucidinostat significantly promoted M1 polarization of macrophages and increased the in vivo antitumor efficacy of aPD-L1. Tucidinostat also enhanced the expression of the costimulatory molecules on human monocytes, suggesting a novel and improved antigen-presenting function.

Conclusions

A combination regimen of tucidinostat and aPD-L1 may work synergistically to reduce tumor burden in patients with cancer by enhancing the immune function and provided a promising treatment strategy to overcome ICI treatment resistance.
How often do cancer researchers make their data and code available and what factors are associated with sharing?
Authors: Hamilton Daniel G. , Page Matthew J. , Finch Sue , Everitt Sarah , Fidler Fiona
Published: November 2022

Background

Various stakeholders are calling for increased availability of data and code from cancer research. However, it is unclear how commonly these products are shared, and what factors are associated with sharing. Our objective was to evaluate how frequently oncology researchers make data and code available and explore factors associated with sharing.

Methods

A cross-sectional analysis of a random sample of 306 cancer-related articles indexed in PubMed in 2019 which studied research subjects with a cancer diagnosis was performed. All articles were independently screened for eligibility by two authors. Outcomes of interest included the prevalence of affirmative sharing declarations and the rate with which declarations connected to data complying with key FAIR principles (e.g. posted to a recognised repository, assigned an identifier, data license outlined, non-proprietary formatting). We also investigated associations between sharing rates and several journal characteristics (e.g. sharing policies, publication models), study characteristics (e.g. cancer rarity, study design), open science practices (e.g. pre-registration, pre-printing) and subsequent citation rates between 2020 and 2021.

Results

One in five studies declared data were publicly available (59/306, 19%, 95% CI: 15–24%). However, when data availability was investigated this percentage dropped to 16% (49/306, 95% CI: 12–20%), and then to less than 1% (1/306, 95% CI: 0–2%) when data were checked for compliance with key FAIR principles. While only 4% of articles that used inferential statistics reported code to be available (10/274, 95% CI: 2–6%), the odds of reporting code to be available were 5.6 times higher for researchers who shared data. Compliance with mandatory data and code sharing policies was observed in 48% (14/29) and 0% (0/6) of articles, respectively. However, 88% of articles (45/51) included data availability statements when required. Policies that encouraged data sharing did not appear to be any more effective than not having a policy at all. The only factors associated with higher rates of data sharing were studying rare cancers and using publicly available data to complement original research.

Conclusions

Data and code sharing in oncology occurs infrequently, and at a lower rate than would be expected given the prevalence of mandatory sharing policies. There is also a large gap between those declaring data to be available, and those archiving data in a way that facilitates its reuse. We encourage journals to actively check compliance with sharing policies, and researchers consult community-accepted guidelines when archiving the products of their research.
Antibiotic-resistant status and pathogenic clonal complex of canine Streptococcus canis-associated deep pyoderma
Authors: Imanishi Ichiro , Iyori Keita , Také Akira , Asahina Ryota , Tsunoi Manami , Hirano Ryuji , Uchiyama Jumpei , Toyoda Yoichi , Sakaguchi Yoshihiko , Hayashi Shunji
Published: November 2022

Background

Streptococcus caniscauses deep pyoderma in canines, which raises concerns about the risk of isolates from lesions acquiring an antibiotic-resistant phenotype. It is necessary to identify effective antibiotics and the characteristics of the pathogenic cluster forS. canis-associated deep pyoderma.

Results

The signalment, molecular typing, and antibiotic-resistant status ofS. canisisolated from deep pyoderma lesions (27 strains) and oral cavities (26 strains) were analyzed. Older dogs tended to haveS. canis-associated deep pyoderma (15 of 27 dogs over 10 years old). Veterinarians chose quinolones for 10/16 cases (63%), even though the rate of quinolone-resistant strains ofS. canisis 38–59%. Although 70% of the strains showed resistance to three or more antibiotic classes (37/53), 94% (50/53) strains showed sensitivity for penicillins. We also identified β-lactamase activity among penicillin-resistant strains ofS. canis. Clonal complex 13 (CC13) was detected only in lesions and formed independent clusters in the phylogenetic tree. One strain of CC13 was resistant to the anti-methicillin-resistantStaphylococcus aureusdrugs, vancomycin and linezolid.

Conclusion

Although antibiotic-resistant strains ofS. canisare isolated at a high rate, they can currently be treated with β-lactamase-inhibiting penicillins. CC13 may be a pathogenic cluster with high levels of antibiotics resistance.
Comparison of machine learning models for bluetongue risk prediction: a seroprevalence study on small ruminants
Authors: Gouda Hagar F. , Hassan Fardos A. M. , El-Araby Eman E. , Moawed Sherif A.
Published: November 2022

Background

Bluetongue (BT) is a disease of concern to animal breeders, so the question on their minds is whether they can predict the risk of the disease before it occurs. The main objective of this study is to enhance the accuracy of BT risk prediction by relying on machine learning (ML) approaches to help in fulfilling this inquiry. Several risk factors of BT that affect the occurrence and magnitude of animal infection with the virus have been reported globally. Additionally, risk factors, such as sex, age, species, and season, unevenly affect animal health and welfare. Therefore, the seroprevalence study data of 233 apparently healthy animals (125 sheep and 108 goats) from five different provinces in Egypt were used to analyze and compare the performance of the algorithms in predicting BT risk.

Results

Logistic regression (LR), decision tree (DT), random forest (RF), and a feedforward artificial neural network (ANN) were used to develop predictive BT risk models and compare their performance to the base model (LR). Model performance was assessed by the area under the receiver operating characteristics curve (AUC), accuracy, true positive rate (TPR), false positive rate (FPR), false negative rate (FNR), precision, and F1 score. The results indicated that RF performed better than other models, with an AUC score of 81%, ANN of 79.6%, and DT of 72.85%. In terms of performance and prediction, LR showed a much lower value (AUC = 69%). Upon further observation of the results, it was discovered that age and season were the most important predictor variables reported in classification and prediction.

Conclusion

The findings of this study can be utilized to predict and control BT risk factors in sheep and goats, with better diagnostic discrimination in terms of accuracy, TPR, FNR, FPR, and precision of ML models over traditional and commonly used LR models. Our findings advocate that the implementation of ML algorithms, mainly RF, in farm decision making and prediction is a promising technique for analyzing cross-section studies, providing adequate predictive power and significant competence in identifying and ranking predictors representing potential risk factors for BT.
Motor neuron survival is associated with reduced neuroinflammation and increased autophagy after brachial plexus avulsion injury in aldose reductase-deficient mice
Authors: Zhong Ke , Huang Yu , Zilundu Prince last Mudenda , Wang Yaqiong , Zhou Yingying , Yu Guangyin , Fu Rao , Chung Sookja Kim , Tang Yamei , Cheng Xiao , Zhou Lihua
Published: November 2022

Brachial plexus root avulsion (BPRA) is frequently caused by high-energy trauma including traffic accident and birth trauma, which will induces massive motoneurons (MNs) death as well as loss of motor and sensory function in the upper limb. The death of MNs is attributed to energy deficiency, neuroinflammation and oxidative stress at the injured ventral horn of spinal cord triggered by BPRA injury. It has been reported which aldose reductase (AR), an endogenous enzyme that catalyzes fructose synthesis, positively correlates with the poor prognosis following cerebral ischemic injury, diabetic retinopathy and diabetic peripheral neuropathy. However, the role of AR in BPRA remains unknown. Herein, we used a mouse model and found that in the spinal cord of BPRA mice, the upregulation of AR correlated significantly with (1) an inactivated SIRT1–AMPK–mTOR pathway and disrupted autophagy; (2) increased byproducts accumulation of lipid peroxidation metabolism and neuroinflammation; and (3) increased MNs death. Furthermore, our results demonstrated the role of AR in BPRA injury whereby the absence of AR (AR knockout mice, AR−/−) prevented the hyper-neuroinflammation and disrupted autophagy as well as motor neuron death caused by BPRA injury. Finally, we further demonstrate that AR inhibitor epalrestat is neuroprotective against BPRA injury by increasing autophagy level, alleviating neuroinflammation and rescuing MNs death in mice. Collectively, our data demonstrate that the AR upregulation in the spinal cord is an important factor contributing to autophagy disruption, neuroinflammation and MNs death following brachial plexus roots avulsion in mice. Our study also provides a promising therapy drug to assist re-implantation surgery for the treatment of BPRA.
Head movement kinematics are altered during balance stability exercises in individuals with vestibular schwannoma
Authors: Zobeiri Omid A. , Wang Lin , Millar Jennifer L. , Schubert Michael C. , Cullen Kathleen E.
Published: November 2022

Background

Balance stabilization exercises are often prescribed to facilitate compensation in individuals with vestibular schwannoma (VS). However, both the assessment and prescription of these exercises are reliant on clinical observations and expert opinion rather than on quantitative evidence. The aim of this study was to quantify head motion kinematics in individuals with vestibular loss while they performed commonly prescribed balance stability exercises.

Methods

Using inertial measurement units, head movements of individuals with vestibular schwannoma were measured before and after surgical deafferentation and compared with age-matched controls.

Results

We found that individuals with vestibular schwannoma experienced more variable head motion compared to healthy controls both pre- and postoperatively, particularly in absence of visual input, but that there was little difference between preoperative and postoperative kinematic measurements for our vestibular schwannoma group. We further found correlations between head motion kinematic measures during balance exercises, performed in the absence of visual input, and multiple clinical measurements for preoperative VS subjects. Subjects with higher head motion variability also had worse DVA scores, moved more slowly during the Timed up and Go and gait speed tests, and had lower scores on the functional gait assessment. In contrast, we did not find strong correlations between clinical measures and postoperative head kinematics for the same VS subjects.

Conclusions

Our data suggest that further development of such metrics based on the quantification of head motion has merit for the assessment and prescription of balance exercises, as demonstrated by the calculation of a “kinematic score” for identifying the most informative balance exercise (i.e., “Standing on foam eyes closed”).
Comprehensive virome analysis of the viral spectrum in paediatric patients diagnosed with Mycoplasma pneumoniae pneumonia
Authors: Guo Qiong , Li Lili , Wang Chao , Huang Yiman , Ma Fenlian , Cong Shanshan , Tan Jingjing , Yao Lihong , Chen Aijun , Zheng Lishu
Published: November 2022

Background

Among hospitalized children suffering from community-acquired pneumonia, Mycoplasma pneumoniae (MP) is one of the most common pathogens. MP often exists as a co-infection with bacteria or viruses, which can exacerbate the clinical symptoms. We investigated the pathogen spectrum in MP-positive and MP-negative samples from hospitalized children with respiratory tract infections in Beijing, China.

Method

This study included 1038 samples of nasopharyngeal aspirates obtained between April, 2017 and March, 2018 from hospitalized children under 6 years of age with respiratory tract infections. To explore the impact of MP infection on the composition of the pathogen spectrum, 185 nasopharyngeal aspirates (83 MP-positive/102 MP-negative) were randomly selected for next-generation sequencing and comprehensive metagenomics analysis. Real-time PCR was used to detect and verify common respiratory viruses.

Results

Of the 1038 samples, 454 (43.7%) were infected with MP. In children < 6 years of age, the MP infection rate gradually increased with age, with the highest rate of 74.2% in 5–6-year-olds. The results of metagenomics analysis revealed 11 human, animal and plant virus families, and bacteriophages, including common respiratory viruses, enteroviruses and anelloviruses. The virus family with the highest number of reads in both MP-positive and MP-negative samples was the Pneumoviridae, and the number of reads for human respiratory syncytial virus (HRSV) in MP-positive samples was higher than that in MP-negative samples. Among the 83 MP-positive samples, 47 (56.63%) were co-infected with viruses, the most common of which was influenza virus (IFV). The durations of hospitalization and fever were higher in patients with MP co-infection than MP single infection, but the difference was not statistically significant.

Conclusion

The viral family with the highest number of reads in both groups was Pneumoviridae, and the number of reads matched to HRSV in MP-positive samples was much higher than MP-negative samples. Co-infection of MP and IFV infection were the most cases.
Carrier frequency and incidence estimation of RPE65-associated inherited retinal diseases in East Asian population by population database-based analysis
Authors: Cho Eun Hye , Park Jong Eun , Lee Taeheon , Ha Kyeongsu , Ki Chang-Seok
Published: November 2022

Background

Inherited retinal diseases (IRDs) are clinically and genetically heterogenous disorders leading to visual impairment and blindness. Because gene therapy for RPE65-associated IRDs was recently approved, it is necessary to predict the carrier frequency and prevalence for RPE65-associated IRDs. This study aimed to analyze the carrier frequency and expected incidence of RPE65-associated IRDs in East Asians and Koreans using exome data from the Genome Aggregation Database (gnomAD) and the Korean Reference Genome Database (KRGDB).

Methods

We analyzed 9,197 exomes for East Asian populations from gnomAD comprising 1,909 Korean and 1,722 Korean genomes from KRGDB. All identified RPE65 variants were classified according to the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines.

Results

The total carrier frequencies of East Asians and Koreans from both gnomAD and KRGDB were 0.10% (11/10,919) and 0.06% (2/3,631), respectively. The estimated incidence of RPE65-associated IRDs was 1/3,941,308 in East Asians and 1/13,184,161 in Koreans.

Conclusion

This study identified carrier frequencies of RPE65-associated IRDs in East Asians and Koreans using gnomAD and KRGDB. We confirmed that the carrier frequency of RPE65-associated IRDs patients was low in Koreans among all East Asian populations, and the incidence was also predicted to be lower than in other East Asian populations. The variant spectrum of RPE65 gene in East Asian and Korean populations differed greatly from those of other ethnic groups.
A global high-density chromatin interaction network reveals functional long-range and trans-chromosomal relationships
Authors: Lohia Ruchi , Fox Nathan , Gillis Jesse
Published: November 2022

Background

Chromatin contacts are essential for gene-expression regulation; however, obtaining a high-resolution genome-wide chromatin contact map is still prohibitively expensive owing to large genome sizes and the quadratic scale of pairwise data. Chromosome conformation capture (3C)-based methods such as Hi-C have been extensively used to obtain chromatin contacts. However, since the sparsity of these maps increases with an increase in genomic distance between contacts, long-range or trans-chromatin contacts are especially challenging to sample.

Results

Here, we create a high-density reference genome-wide chromatin contact map using a meta-analytic approach. We integrate 3600 human, 6700 mouse, and 500 fly Hi-C experiments to create species-specific meta-Hi-C chromatin contact maps with 304 billion, 193 billion, and 19 billion contacts in respective species. We validate that meta-Hi-C contact maps are uniquely powered to capture functional chromatin contacts in both cis and trans. We find that while individual dataset Hi-C networks are largely unable to predict any long-range coexpression (median 0.54 AUC), meta-Hi-C networks perform comparably in both cis and trans (0.65 AUC vs 0.64 AUC). Similarly, for long-range expression quantitative trait loci (eQTL), meta-Hi-C contacts outperform all individual Hi-C experiments, providing an improvement over the conventionally used linear genomic distance-based association. Assessing between species, we find patterns of chromatin contact conservation in both cis and trans and strong associations with coexpression even in species for which Hi-C data is lacking.

Conclusions

We have generated an integrated chromatin interaction network which complements a large number of methodological and analytic approaches focused on improved specificity or interpretation. This high-depth “super-experiment” is surprisingly powerful in capturing long-range functional relationships of chromatin interactions, which are now able to predict coexpression, eQTLs, and cross-species relationships. The meta-Hi-C networks are available at https://labshare.cshl.edu/shares/gillislab/resource/HiC/.
Brief Educational Workshops in Secondary Schools Trial (BESST): protocol for a school-based cluster randomised controlled trial of open-access psychological workshop programme for 16–18-year-olds
Authors: Lisk Stephen , Carter Ben , James Kirsty , Stallard Paul , Deighton Jessica , Yarrum Jynna , Fonagy Peter , Day Crispin , Byford Sarah , Shearer James , Weaver Timothy , Sclare Irene , Evans Claire , Farrelly Maria , Ho Pin-Cheng , Brown June ,   BESST Study Collaborators
Published: November 2022

Anxiety and depression are increasingly prevalent in adolescents, often causing daily distress and negative long-term outcomes. Despite the significant and growing burden, less than 25% of those with probable diagnosis of anxiety and depression are receiving help in England. Significant barriers to help-seeking exist in this population, with a scarcity of easily accessible, effective, and cost-effective interventions tailored specially for this age group. One intervention that has been shown to be feasible to deliver and with the promise of reducing stress in this age group is a school-based stress workshop programme for 16–18-year-olds (herein called DISCOVER). The next step is to rigorously assess the effectiveness, and cost-effectiveness, of the DISCOVER intervention in a fully powered cluster randomised controlled trial (cRCT). If found to be clinically and cost-effective, DISCOVER could be scaled up as a service model UK-wide and have a meaningful impact on the mental health of adolescents across the country.

Trial registration: ISRCTN registry ISRCTN90912799. Registered with ISRCTN 28 May 2020.
The Workwell trial: protocol for the process evaluation of a randomised controlled trial of job retention vocational rehabilitation for employed people with inflammatory arthritis
Authors: Hammond Alison , Radford Kathryn A. , Ching Angela , Prior Yeliz , O’Brien Rachel , Woodbridge Sarah , Culley June , Parker Jennifer , Holland Paula
Published: November 2022

Background

The Workwell trial is a multi-centre randomised controlled trial with the aims of evaluating the effectiveness and cost-effectiveness of job retention vocational rehabilitation for employed people with inflammatory arthritis, who are experiencing work difficulties due to their arthritis. Vocational rehabilitation is delivered by health service occupational therapists, who have received additional training in providing this Workwell intervention. A process evaluation will be undertaken alongside the main trial to investigate implementation fidelity; understand key stakeholders’ perspectives of the intervention and the social and structural context in which the intervention is provided; and explore issues related to future implementation in clinical practice. This protocol describes the aims, objectives, and methodology of the Workwell trial process evaluation.

Methods

This mixed methods process evaluation will follow the Medical Research Council’s Guidance on process evaluations for complex interventions. It will be underpinned by the conceptual framework for implementation fidelity (CFIF) and normalisation process theory (NPT). We will analyse treatment records, work assessments, and treatment notes to ascertain implementation fidelity. Semi-structured interviews with trial participants, their employer/line managers, treating therapists, and their therapy service managers will be undertaken to explore perceptions of the intervention, contextual factors, and potential for future implementation in practice. Interview topic guides will be informed by NPT. Therapists’ views about Workwell training will be explored via questionnaires following training, and interviews and focus groups following treatment delivery to inform future implementation. Quantitative data will be analysed descriptively. Qualitative data will be analysed using thematic analysis. NPT will guide data analysis and interpretation. Findings from the different elements of this embedded design process evaluation will be reported separately and then the elements integrated. The process evaluation data will be analysed independently of the Workwell trial outcome evaluation. The process evaluation data will then be reviewed in the light of the trial findings.

Discussion

Few trials of job retention vocational rehabilitation in arthritis have included process evaluations. This process evaluation will assist in understanding factors influencing trial outcomes and identifying potential contextual barriers and facilitators for the potential implementation of Workwell vocational rehabilitation into clinical services.

Trial registration

ClinicalTrials.gov NCT03942783. Registered on 08 May 2019. ISRCTN Registry ISRCTN61762297. Registered on 13 May 2019. Retrospectively registered.
A new version of $( p,q ) $-Hermite–Hadamard’s midpoint and trapezoidal inequalities via special operators in $( p,q ) $-calculus
Authors: Sitthiwirattham Thanin , Ali Muhammad Aamir , Budak Hüseyin , Etemad Sina , Rezapour Shahram
Published: November 2022

In this paper, we conduct a research on a new version of the$( p,q ) $(p,q)-Hermite–Hadamard inequality for convex functions in the framework of postquantum calculus. Moreover, we derive several estimates for$(p,q)$(p,q)-midpoint and$(p,q)$(p,q)-trapezoidal inequalities for special$( p,q ) $(p,q)-differentiable functions by using the notions of left and right$(p,q ) $(p,q)-derivatives. Our newly obtained inequalities are extensions of some existing inequalities in other studies. Lastly, we consider some mathematical examples for some$(p,q)$(p,q)-functions to confirm the correctness of newly established results.
Vaccination coverage in Italian children and antimicrobial resistance: an ecological analysis
Authors: Maugeri Andrea , Barchitta Martina , Agodi Antonella
Published: November 2022

Background

Although a general consensus that vaccines could be a complementary strategy against antimicrobial resistance (AMR), there is still the need for studies investigating the relationship between childhood vaccination coverage and AMR proportions in the overall population.

Methods

We performed an ecological analysis of available Italian data (vaccination coverages, AMR proportions, number of isolates tested, and antibiotic use) to evaluate the relationships between vaccination coverages in children and AMR proportions in the last 2 decades.

Results

After adjusting for covariates, we showed that AMR proportions decreased with increasing vaccination coverages, especially for some combinations of vaccines, pathogens, and antimicrobials. Vaccination coverages for pertussis, diphtheria, and tetanus were inversely related to proportions of E. coli resistant to fluoroquinolones and third generation cephalosporins, K. pneumoniae resistant to carbapenems and third generation cephalosporins, and P. aeruginosa resistant to piperacillin and tazobactam. Polio vaccination coverage was inversely related to proportions of E. coli and K. pneumoniae resistant to third generation cephalosporins.

Conclusions

These results, however, should be interpreted cautiously due to the ecological nature of our analysis. For this reason, further studies designed ad hoc should be encouraged to measure the impact of increasing childhood vaccination coverage on AMR.
The optimal neoadjuvant chemotherapy regimen for locally advanced gastric and gastroesophageal junction adenocarcinoma: a systematic review and Bayesian network meta-analysis
Authors: Wang Tongya , Li Changyang , Li Xiang , Zhai Jing , Wang Shoulin , Shen Lizong
Published: November 2022

Background

Neoadjuvant chemotherapy (NAC) for locally advanced gastric and gastroesophageal junction adenocarcinoma (LAGC) has been recommended in several guidelines. However, there is no global consensus about the optimum of NAC regimens. We aimed to determine the optimal NAC regimen for LAGC.

Methods

A systematic review and Bayesian network meta-analysis was performed. The literature search was conducted from inception to June 2022. The odds ratio (OR) value and 95% confidence interval (95% CI) were used for assessment of R0 resection rate and pathological complete response rate (pCR) as primary outcomes. The hazard ratio (HR) value and 95% CI were interpreted for the assessment of overall survival (OS) and disease-free survival (DFS) as second outcomes. The risk ratio (RR) value and 95% CI were used for safety assessment.

Results

Twelve randomized controlled trials were identified with 3846 eligible participants. The network plots for R0 resectability, OS, and DFS constituted closed loops. The regimens of TPF (taxane and platinumplusfluoropyrimidine), ECF (epirubicin and cisplatinplusfluorouracil), and PF (platinumplusfluoropyrimidine) showed a meaningful improvement of R0 resectability, as well as OS and/or DFS, compared with surgery (including surgery-alone and surgerypluspostoperative adjuvant chemotherapy). Importantly, among these regimens, TPF regimen showed significant superiority in R0 resection rate (versusECF regimen), OS (versusECF regimen), DFS (versusPF and ECF regimens), and pCR (versusPF regimen).

Conclusions

The taxane-based triplet regimen of TPF is likely the optimal neoadjuvant chemotherapy regimen for LAGC patients.
Sex differences in heart: from basics to clinics
Authors: Prajapati Chandra , Koivumäki Jussi , Pekkanen-Mattila Mari , Aalto-Setälä Katriina
Published: November 2022

Sex differences exist in the structure and function of human heart. The patterns of ventricular repolarization in normal electrocardiograms (ECG) differ in men and women: men ECG pattern displays higher T-wave amplitude and increased ST angle. Generally, women have longer QT duration because of reduced repolarization reserve, and thus, women are more susceptible for the occurrence of torsades de pointes associated with drugs prolonging ventricular repolarization. Sex differences are also observed in the prevalence, penetrance and symptom severity, and also in the prognosis of cardiovascular disease. Generally, women live longer, have less clinical symptoms of cardiac diseases, and later onset of symptoms than men. Sex hormones also play an important role in regulating ventricular repolarization, suggesting that hormones directly influence various cellular functions and adrenergic regulation. From the clinical perspective, sex-based differences in heart physiology are widely recognized, but in daily practice, cardiac diseases are often underdiagnosed and untreated in the women. The underlying mechanisms of sex differences are, however, poorly understood. Here, we summarize sex-dependent differences in normal cardiac physiology, role of sex hormones, and differences in drug responses. Furthermore, we also discuss the importance of human induced pluripotent stem cell-derived cardiomyocytes in further understanding the mechanism of differences in women and men.