bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting selenoprotein H in the nucleolus suppresses tumors and metastases by Isovalerylspiramycin I
Authors: Cui Jing , Zhou Jingcheng , He Weiqing , Ye Juan , Westlake Timothy , Medina Rogelio , Wang Herui , Thakur Bhushan L. , Liu Juanjuan , Xia Mingyu , He Zhonggui , Indig Fred E. , Li Aiguo , Li Yan , Weil Robert J. , Aladjem Mirit I. , Zhong Laiping , Gilbert Mark R. , Zhuang Zhengping 
Published: April 2022

Abstract
Background
Compared to normal cells, cancer cells exhibit a higher level of oxidative stress, which primes key cellular and metabolic pathways and thereby increases their resilience under oxidative stress. This higher level of oxidative stress also can be exploited to kill tumor cells while leaving normal cells intact. In this study we have found that isovalerylspiramycin I (ISP I), a novel macrolide antibiotic, suppresses cancer cell growth and tumor metastases by targeting the nucleolar protein selenoprotein H (SELH), which plays critical roles in keeping redox homeostasis and genome stability in cancer cells.

Methods
We developed ISP I through genetic recombination and tested the antitumor effects using primary and metastatic cancer models. The drug target was identified using the drug affinity responsive target stability (DARTS) and mass spectrum assays. The effects of ISP I were assessed for reactive oxygen species (ROS) generation, DNA damage, R-loop formation and its impact on the JNK2/TIF-IA/RNA polymerase I (POLI) transcription pathway.

Results
ISP I suppresses cancer cell growth and tumor metastases by targeting SELH. Suppression of SELH induces accumulation of ROS and cancer cell-specific genomic instability. The accumulation of ROS in the nucleolus triggers nucleolar stress and blocks ribosomal RNA transcription via the JNK2/TIF-IA/POLI pathway, causing cell cycle arrest and apoptosis in cancer cells.

Conclusions
We demonstrated that ISP I links cancer cell vulnerability to oxidative stress and RNA biogenesis by targeting SELH. This suggests a potential new cancer treatment paradigm, in which the primary therapeutic agent has minimal side-effects and hence may be useful for long-term cancer chemoprevention.
Knockdown resistance (kdr) gene of Aedes aegypti in Malaysia with the discovery of a novel regional specific point mutation A1007G
Authors: Akhir Mas Azlin M. , Wajidi Mustafa F. F. , Lavoué Sébastien , Azzam Ghows , Jaafar Izhan Shahrin , Awang Besar Noor Aslinda Ummi , Ishak Intan H. 
Published: April 2022

Abstract
Background
Improved understanding of the molecular basis of insecticide resistance may yield new opportunities for control of relevant disease vectors. In this current study, we investigated the quantification responses for the phenotypic and genotypic resistance of Aedes aegypti populations from different states in Malaysia.

Methods
We tested the insecticide susceptibility status of adult Ae. aegypti from populations of three states, Penang, Selangor and Kelantan (Peninsular Malaysia), against 0.25% permethrin and 0.25% pirimiphos-methyl using the World Health Organisation (WHO) adult bioassay method. Permethrin-resistant and -susceptible samples were then genotyped for domains II and III in the voltage-gated sodium channel (vgsc) gene using allele-specific polymerase chain reaction (AS-PCR) for the presence of any diagnostic single-nucleotide mutations. To validate AS-PCR results and to identify any possible additional point mutations, these two domains were sequenced.

Results
The bioassays revealed that populations of Ae. aegypti from these three states were highly resistant towards 0.25% permethrin and 0.25% pirimiphos-methyl. Genotyping results showed that three knockdown (kdr) mutations (S989P, V1016G and F1534C) were associated with pyrethroid resistance within these populations. The presence of a novel mutation, the A1007G mutation, was also detected.

Conclusions
This study revealed the high resistance level of Malaysian populations of Ae. aegypti to currently used insecticides. The resistance could be due to the widespread presence of four kdr mutations in the field and this could potentially impact the vector control programmes in Malaysia and alternative solutions should be sought.

Graphical Abstract
Successful treatment of an infant with congenital bile acid synthesis disorder type 3 by ursodeoxycholic acid: a case report
Authors: Mo Weiqian , Wang Feng , Zhou Chuanen , Ma Tinghe , Pan Zhaojun , Xie Min , Ren Haoyan , Xie Yongwu 
Published: April 2022

Abstract
Background
Congenital bile acid synthesis disorder type 3 caused by oxysterol 7α-hydroxylase deficiency is an extremely rare genetic liver disease. As it may cause rapid progression to end-stage liver disease, a high cautiousness in diagnosis and early treatment are required. Here we describe the first case of congenital bile acid synthesis disorder type 3 in China that was confirmed by genetic analysis.

Case presentation
A 5-month-old Chinese male infant suffered skin yellowing since birth. The patient showed significantly increased alanine transaminase, aspartate transaminase, and total and direct bilirubin levels, and enlarged liver at admission. Whole-exome sequencing confirmed homozygous mutation in the CYB7B1 gene that encodes oxysterol 7α-hydroxylase. Ursodeoxycholic acid treatment significantly mitigated the condition of the patient and lowered biochemical indicators. Unfortunately, the patient developed septicemia and gave up treatment.

Conclusions
The patient was successfully treated with ursodeoxycholic acid, which has not been reported previously. Ursodeoxycholic acid replacement therapy is an effective and affordable treatment for congenital bile acid synthesis disorder type 3 caused by oxysterol 7α-hydroxylase deficiency.
The effect of FK506 (tacrolimus) loaded with collagen membrane and fibrin glue on promotion of nerve regeneration in a rat sciatic nerve traction injury model
Authors: Kim Jin-Hong , Choi Young-Jin , Park Han-Ick , Ahn Kang-Min 
Published: April 2022

Abstract
Background
Peripheral nerve injury is one of the most common injuries that might occur in oral and maxillofacial surgery. The purpose of this study was to determine the effect of FK506 loaded with collagen membrane and fibrin glue on the promotion of nerve regeneration after traction nerve injury in a rat model.

Methods
Thirty male Sprague-Dawley rats were divided into three groups: group A (n = 10), a sham group whose sciatic nerve was exposed without any injury; and groups B (n = 10) and C (n = 10), which underwent traction nerve injury using 200 g of traction force for 1 min. The injured nerve in group C was covered with a collagen membrane soaked with FK506 (0.5 mg/0.1 mL) and fibrin glue. Functional analysis and microscopic evaluation were performed at 2 and 4 weeks after injury.

Results
The sciatic function index was − 5.78 ± 3.07 for group A, − 20.69 ± 5.22 for group B, and − 12.01 ± 4.20 for group C at 2 weeks after injury. However, at 4 weeks, the sciatic function index was − 5.58 ± 2.45 for group A, − 19.69 ± 4.81 for group B, and − 11.95 ± 1.94 for group C. In both periods, statistically significant differences were found among the groups (p<0.017). Histomorphometric evaluation revealed improved nerve regeneration in group C compared to that in group B. However, no statistical differences in axonal density were found among the three groups (p < 0.017).

Conclusion
Localized FK506 with collagen membrane and fibrin glue could promote axonal regeneration in a rat model of traction nerve injury.
Risk of Cardiovascular Disease in Women With and Without Breast Cancer: The Pathways Heart Study
Authors: Greenlee Heather , Iribarren Carlos , Rana Jamal S. , Cheng Richard , Nguyen-Huynh Mai , Rillamas-Sun Eileen , Shi Zaixing , Laurent Cecile A. , Lee Valerie S. , Roh Janise M. , Santiago-Torres Margarita , Shen Hanjie , Hershman Dawn L. , Kushi Lawrence H. , Neugebauer Romain , Kwan Marilyn L. 
Published: April 2022

PURPOSE To examine cardiovascular disease (CVD) and mortality risk in women with breast cancer (BC) by cancer therapy received relative to women without BC. METHODS The study population comprised Kaiser Permanente Northern California members. Cases with invasive BC diagnosed from 2005 to 2013 were matched 1:5 to controls without BC on birth year and race/ethnicity. Cancer treatment, CVD outcomes, and covariate data were from electronic health records. Multivariable Cox proportional hazards models estimated hazard ratios (HRs) and 95% CIs of CVD incidence and mortality by receipt of chemotherapy treatment combinations, radiation therapy, and endocrine therapy. RESULTS A total of 13,642 women with BC were matched to 68,202 controls without BC. Over a 7-year average follow-up (range < 1-14 years), women who received anthracyclines and/or trastuzumab had high risk of heart failure/cardiomyopathy relative to controls, with the highest risk seen in women who received both anthracyclines and trastuzumab (HR, 3.68; 95% CI, 1.79 to 7.59). High risk of heart failure and/or cardiomyopathy was also observed in women with BC with a history of radiation therapy (HR, 1.38; 95% CI, 1.13 to 1.69) and aromatase inhibitor use (HR, 1.31; 95% CI, 1.07 to 1.60), relative to their controls. Elevated risks for stroke, arrhythmia, cardiac arrest, venous thromboembolic disease, CVD-related death, and death from any cause were also observed in women with BC on the basis of cancer treatment received. CONCLUSION Women with BC had increased incidence of CVD events, CVD-related mortality, and all-cause mortality compared with women without BC, and risks varied according to the history of cancer treatment received. Studies are needed to determine how women who received BC treatment should be cared for to improve cardiovascular outcomes.
Surgeon-Led Initiatives to Increase Access to Surgical Treatment of Epilepsy at an Academic Level 4 Epilepsy Center: An Observational Cohort Study
Authors: Cole Tyler S. , Vadera Sumeet 
Published: April 2022

BACKGROUND:
Underutilization of surgical treatment for epilepsy is multifactorial, and the multidisciplinary nature of caring for these patients represents a significant hurdle in expanding surgical treatment of epilepsy.

OBJECTIVE:
To develop internal and external surgical referral relationships for patients with medically refractory epilepsy with the goal of improving access to care.

METHODS:
To expand access to surgical epilepsy treatment at University of California (UC)–Irvine, 4 broad approaches focused on developing referral relationships and process improvement of surgical evaluation were undertaken in 2015 and 2016. The authors performed a retrospective review of all surgical epilepsy case referrals of the senior author from 2014 through 2020.

RESULTS:
Epilepsy surgical volume at UC–Irvine increased from an average of 5.2 cases annually to 32 cases in the first year (2015) of implementation. There was continued case volume growth from 2015 through 2020 to 52 procedures in the most recent year (P = .03). Hospital payments for epilepsy procedures increased from $1.09M in 2015 to $2.02M and $1.8M in 2019 and 2020 (P < .01), respectively, while maintaining a diverse payer mix. 79.4% of these patients did not have a previously established option for surgical epilepsy care.

CONCLUSION:
We outline strategies that level 4 epilepsy centers may use to strengthen collaborations and improve patient access for surgical epilepsy treatment. Increased collaboration can both improve the number of patients with epilepsy with access to specialized surgical care and produce reimbursement benefits for the centers caring for these patients, regardless of insurance source.
Nursing home-sensitive conditions: analysis of routine health insurance data and modified Delphi analysis of potentially avoidable hospitalizations
Authors: Bohnet-Joschko Sabine , Valk-Draad Maria Paula , Schulte Timo , Groene Oliver 
Published: April 2022

Background: Hospitalizations of nursing home residents are associated with various health risks. Previous research indicates that, to some extent, hospitalizations of this vulnerable population may be inappropriate and even avoidable. This study aimed to develop a consensus list of hospital discharge diagnoses considered to be nursing home-sensitive, i.e., avoidable.Methods: The study combined analyses of routine data from six statutory health insurance companies in Germany and a two-stage Delphi panel, enhanced by expert workshop discussions, to identify and corroborate relevant diagnoses. Experts from four different disciplines estimated the proportion of hospitalizations that could potentially have been prevented under optimal conditions. Results: We analyzed frequencies and costs of data for hospital admissions from 242,236 nursing home residents provided by statutory health insurance companies. We identified 117 hospital discharge diagnoses, which had a frequency of at least 0.1%. We recruited experts (primary care physicians, hospital specialists, nursing home professionals and researchers) to estimate the proportion of potentially avoidable hospitalizations for the 117 diagnoses deemed avoidable in two Delphi rounds (n=107 in Delphi Round 1 and n=96 in Delphi Round 2, effective response rate=91%). A total of 35 diagnoses with high and consistent estimates of the proportion of potentially avoidable hospitalizations were identified as nursing home-sensitive. In an expert workshop (n=16), a further 25 diagnoses were discussed that had not reached the criteria, of which another 23 were consented to be nursing home-sensitive conditions. Extrapolating the frequency and mean costs of these 58 diagnoses to the national German context yielded total potentially avoidable care costs of €768,304,547, associated with 219,955 nursing home-sensitive hospital admissions.Conclusion: A total of 58 nursing home-relevant diagnoses (ICD-10-GM three-digit level) were classified as nursing home-sensitive using an adapted Delphi procedure. Interventions should be developed to avoid hospital admission from nursing homes for these diagnoses.
Incentivising research data sharing: a scoping review
Authors: Woods Helen Buckley , Pinfield Stephen 
Published: April 2022

Background: Numerous mechanisms exist to incentivise researchers to share their data. This scoping review aims to identify and summarise evidence of the efficacy of different interventions to promote open data practices and provide an overview of current research. Methods: This scoping review is based on data identified from Web of Science and LISTA, limited from 2016 to 2021. A total of 1128 papers were screened, with 38 items being included. Items were selected if they focused on designing or evaluating an intervention or presenting an initiative to incentivise sharing. Items comprised a mixture of research papers, opinion pieces and descriptive articles. Results: Seven major themes in the literature were identified: publisher/journal data sharing policies, metrics, software solutions, research data sharing agreements in general, open science ‘badges’, funder mandates, and initiatives. Conclusions: A number of key messages for data sharing include: the need to build on existing cultures and practices, meeting people where they are and tailoring interventions to support them; the importance of publicising and explaining the policy/service widely; the need to have disciplinary data champions to model good practice and drive cultural change; the requirement to resource interventions properly; and the imperative to provide robust technical infrastructure and protocols, such as labelling of data sets, use of DOIs, data standards and use of data repositories.
Improving delirium screening in older adults at the Royal United Hospital, Bath
Authors: Trew Christopher AJ , Cross Rachael , Howell Kate , Dyer Chris 
Published: April 2022

Aims/Background Delirium affects around 20% of older inpatients, increasing mortality and length of stay. Around 30% of cases are preventable. The authors sought to determine compliance of the admissions to the Older People's Unit of the Royal University Hospital Bath with the national and internal guidelines for delirium screening and improve its use on admission. Methods A total of 60 patients' notes were inspected for compliance. Subsequently, the authors implemented teaching, changed the admission proforma and re-wrote the hospital guidelines for delirium. The notes were rescreened at 6 and 18 months. Results Initially, 25% of notes met the national standards and 63% met the hospital criteria. At 6 months this was 52% and 82% respectively, and at 18 months it was 41% and 87% respectively. The proportion of patients screened via multiple methods also increased. Conclusions There was a sustained improvement in compliance with the national and hospital standards for delirium screening. There was some degradation in the national standard but the proportion of patients meeting the National Institute for Health and Care Excellence standard was still higher than pre-intervention.
Task-related trunk training on balance, trunk control, pulmonary function and quality of life in patients with Parkinson's disease. A randomised controlled trial
Authors: Akhila RM , Karthikbabu Suruliraj , Mohan Divya , Prem Venkatesan , Roy Ajith Kumar 
Published: April 2022

Background/Aims Stooped posture and ‘en-bloc’ movement of the trunk in people with Parkinson's disease are related to balance issues, pulmonary dysfunction and difficulty in daily tasks. The primary objective of this study was to examine the effects of task-related trunk training on balance in people with Parkinson's disease. The secondary objective was to observe whether trunk control, thoracic rotation range, pulmonary function and quality of life would change for patients with Parkinson's disease after trunk training. Methods A total of 32 individuals participated in this randomised controlled trial. They had a mean age of 70.8 years, with a modified Hoehn and Yahr Scale grade of 1.5–3, could take more than six steps in the 360° turn test, were scored as grade I or II on the retropulsion test and had an absence of severe cognitive deficits. Task-related trunk training emphasised the thoracic spine's extension and rotation in prone position on elbows, hands and knees and in kneeling, sitting and standing positions. Standard physiotherapy included breathing exercises, stretching of shoulder and neck muscles, balance and walking training. Both groups practised for 1 hour a day, 3 days a week over 6 weeks. The primary outcome measure was the Mini-Balance Evaluation Systems Test. The secondary outcome measures were the Trunk Control Test, thoracic rotation range of movement, Pulmonary Function Test and Parkinson's Disease Questionnaire-39. Results Repeated measure analysis of variance revealed significant group by time interaction for the Mini-Balance Evaluation Systems Test and thoracic rotation range (P<0.05), but not for the pulmonary function test and quality of life measures. Conclusions Task-related trunk training appears to be more beneficial in the balance capacity of individuals with Parkinson's disease than standard physiotherapy, but does not have any significant effects for pulmonary function and health-related quality of life.
Exercise modifies the disease-relevant gut microbial shifts in post-traumatic osteoarthritis rats
Authors: Hao Xiaoxia , Zhang Jiaming , Shang Xingru , Sun Kai , Zhou Jun , Liu Jiawei , Chi Ruimin , Xu Tao 
Published: April 2022

Aims Post-traumatic osteoarthritis (PTOA) is a subset of osteoarthritis (OA). The gut microbiome is shown to be involved in OA. However, the effect of exercise on gut microbiome in PTOA remains elusive. Methods A total of 18 eight-week Sprague-Dawley rats were assigned into three groups: Sham/sedentary (Sham/Sed), PTOA/sedentary (PTOA/Sed), and PTOA/treadmill-walking (PTOA/TW). PTOA model was induced by transection of the anterior cruciate ligament (ACLT) and the destabilization of the medial meniscus (DMM). Treadmill-walking (15 m/min, 30 min/d, five days/week for eight weeks) was employed in the PTOA/TW group. The response of cartilage, subchondral bone, serology, and gut microbiome and their correlations were assessed. Results Eight-week treadmill-walking was effective at maintaining the integrity of cartilage-subchondral bone unit and reducing the elevated systematic inflammation factors and microbiome-derived metabolites. Furthermore, 16S ribosomal ribonucleic acid (rRNA) sequencing showed disease-relevant microbial shifts in PTOA animals, characterized by the decreased abundance of phylum TM7 and the increase of phylum Fusobacteria. At the genus level, the abundance of Lactobacillus, Turicibacter, Adlercreutzia, and Cetobacterium were increased in the PTOA animals, while the increase of Adlercreutzia and Cetobacterium was weakened as a response to exercise. The correlation analysis showed that genus Lactobacillus and Adlercreutzia were correlated to the structural OA phenotypes, while phylum Fusobacteria and genus Cetobacterium may contribute to the effects of exercise on the diminishment of serological inflammatory factors. Conclusion Exercise is effective at maintaining the integrity of cartilage-subchondral bone unit, and the exercise-induced modification of disease-relevant microbial shifts is potentially involved in the mechanisms of exercise-induced amelioration of PTOA. Cite this article: Bone Joint Res 2022;11(4):214–225.
The clinical demand and supply of blood in India: A National level estimation study
Authors: Mammen Joy John , Asirvatham Edwin Sam , Lakshmanan Jeyaseelan , Sarman Charishma Jones , Pandey Arvind , Ranjan Varsha , Charles Bimal , Mani Thenmozhi , Khaparde Sunil D , Upadhyaya Sunita , Rajan Shobini 
Published: April 2022

Background
Estimating the clinical demand for blood and components arising in a health facility is crucial to ensure timely availability of blood. This study aims to estimate disease-specific clinical demand, supply and utilization of whole blood and components in India.

Methods
We conducted a national level cross-sectional study in five randomly selected states from five regions of the country. We included 251 public and private facilities representing primary, secondary and tertiary care facilities. We collected annual disease-specific demand, supply and utilization of blood and components using a structured tool. We estimated the national demand by extrapolating the study data (demand and beds) to the total number of estimated beds in the country.

Findings
According to the study, the total clinical demand of 251 health facilities with 51,562 beds was 474,627 whole blood units. Based on this, the clinical demand for India was estimated at 14·6 million whole blood units (95 CI: 14·59–14·62), an equivalent of 36·3 donations per 1,000 eligible populations, which will address whole blood and component requirement. The medicine specialty accounted for 6·0 million units (41·2%), followed by surgery 4·1 million (27·9%), obstetrics and gynecology 3·3 million (22·4%) and pediatrics 1·2 million (8·5%) units. The supply was 93% which is equivalent to 33·8 donations against the demand.

Conclusion
The study indicated a demand and supply gap of 2.5 donations per 1,000 eligible persons which is around one million units. The gap emphasises the need for sustained and concerted efforts from all stakeholders and for increasing the awareness about repeat voluntary non-remunerated blood donation (VNRBD); optimizing the availability of blood components through efficient blood component separation units; promoting modern principles of patient blood management and strengthening capacities of human resources in the blood transfusion system in India.