bluuebunny/crossref_metadata_2025_split huggingface dataset:
In-situ TiO2-x decoration of titanium carbide MXene for photo/sono-responsive antitumor theranostics
Authors: Zhang Dong-Yang , Liu Hengke , Younis Muhammad Rizwan , Lei Shan , Chen Yunzhi , Huang Peng , Lin Jing 
Published: January 2022

Abstract
Background
Sonodynamic therapy (SDT) has emerged as a noninvasive therapeutic modality that involves sonosensitizers and low-intensity ultrasound. However, owing to the rapid recombination of charge carriers, most of the sonosensitizers triggered poor reactive oxygen species (ROS) generation, resulting in unsatisfactory sonodynamic therapeutic effects.

Results
Herein, a photo/sono-responsive nanoplatform was developed through the in-situ systhesis of TiO2-x on the surface of two-dimensional MXene (titanium carbide, Ti3C2) for photoacoustic/photothermal bimodal imaging-guided near-infrared II (NIR-II) photothermal enhanced SDT of tumor. Because of several oxygen vacancies and smaller size (~ 10 nm), the in-situ formed TiO2-x nanoparticles possessed narrow band gap (2.65 eV) and high surface area, and thus served as a charge trap to restrict charge recombination under ultrasound (US) activation, resulting in enhanced sonodynamic ROS generation. Moreover, Ti3C2 nanosheets induced extensive localized hyperthermia relieves tumor hypoxia by accelerating intratumoral blood flow and tumor oxygenation, and thus further strengthened the efficacy of SDT. Upon US/NIR-II laser dual-stimuli, Ti3C2@TiO2-x nanoplatform triggered substantial cellular killing in vitro and complete tumor eradication in vivo, without any tumor recurrence and systemic toxicity.

Conclusion
Our work presents the promising design of photo/sono-responsive nanoplatform for cancer nanotheranostics.

Graphical Abstract
Novel bi-allelic MSH4 variants causes meiotic arrest and non-obstructive azoospermia
Authors: Li Peng , Ji Zhiyong , Zhi Erlei , Zhang Yuxiang , Han Sha , Zhao Liangyu , Tian Ruhui , Chen Huixing , Huang Yuhua , Zhang Jing , Chen Huirong , Zhao Fujun , Zhou Zhi , Li Zheng , Yao Chencheng 
Published: January 2022

Abstract
Background
Non-obstructive azoospermia (NOA) is one of the most severe type in male infertility, and the genetic causes of NOA with meiotic arrest remain elusive.

Methods
Four Chinese families with NOA participated in the study. We performed whole-exome sequencing (WES) for the four NOA-affected patients in four pedigrees. The candidate causative gene was further verified by Sanger sequencing. Hematoxylin and eosin staining (H&E) and immunohistochemistry (IHC) were carried out to evaluate the stage of spermatogenesis arrested in the patients with NOA.

Results
We identified two novel homozygous frameshift mutations of MSH4 and two novel compound heterozygous variants in MSH4 in four pedigrees with NOA. Homozygous loss of function (LoF) variants in MSH4 was identified in the NOA-affected patient (P9359) in a consanguineous Chinese family (NM_002440.4: c.805_812del: p.V269Qfs*15) and one patient with NOA (P21504) in another Chinese family (NM_002440.4: c.2220_2223del:p.K741Rfs*2). Also, compound heterozygous variants in MSH4 were identified in two NOA-affected siblings (P9517 and P9517B) (NM_002440.4: c.G1950A: p.W650X and c.2179delG: p.D727Mfs*11), and the patient with NOA (P9540) (NM_002440.4: c.G244A: p.G82S and c.670delT: p.L224Cfs*3). Histological analysis demonstrated lack of spermatozoa in seminiferous tubules of all patients and IHC showed the spermatogenesis arrested at the meiotic prophase I stage. Consistent with the autosomal recessive mode of inheritance, all of these mutations were inherited from heterozygous parental carriers.

Conclusions
We identified that six novel mutations in MSH4 responsible for meiotic arrest and NOA. And these results provide researchers with a new insight to understand the genetic etiology of NOA and to identify new loci for genetic counselling of NOA.
Applying WHO COVID-19 workforce estimate tools remotely in an African context: a case report from Mali and Kenya
Authors: McQuide Pamela A. , Finnegan Amy , Terry Katherine M. , Brown Andrew , Toure Cheick Oumar , Tessougue Jeanne , Cisse Ibrahim , Thuku Mathew Kariuki , Muriuki Janet , Ochola Mary , Ogato Julius , Coulibaly Etienne , Togora Toure Djeneba 
Published: January 2022

Abstract
Background
The COVID-19 pandemic has increased the burden on health systems, particularly in low- and middle-income countries, where health systems already struggle. To meet health workforce planning needs during the pandemic, IntraHealth International used two tools created by the World Health Organization (WHO) Regional Office for Europe. The Health Workforce Estimator (HWFE) allows the estimation of the quantity of health workers needed to treat patients during a surge, and the Adaptt Surge Planning Support Tool helps to predict the timing of a surge in cases and the number of health workers and beds needed for predicted caseload. These tools were adapted to fit the African context in a rapid implementation over 5 weeks in one region in Mali and one region in Kenya with the objective to test the feasibility of adapting these tools, which use a Workload Indicators of Staffing Need (WISN)-inspired human resources management methodology, to obtain daily and surge projections of COVID-19 human resources for health needs.

Case presentation
Using a remote team in the US and in-country teams in Mali and Kenya, IntraHealth enacted a phased plan to gather stakeholder support, collect data related to health systems and COVID-19 cases, populate data into the tools, verify modeled results with results on the ground, enact policy measures to meet projected needs, and conduct national training workshops for the ministries of health.

Conclusions
This phased implementation in Mali and Kenya demonstrated that the WISN approach applied to the Health Workforce Estimator and Adaptt tools can be readily adapted to the local context for African countries to rapidly estimate the number of health workers and beds needed to respond to the predicted COVID-19 pandemic caseload. The results may also be used to give a proxy estimate for needed health supplies—e.g., oxygen, medications, and ventilators. Challenges included accurate and timely data collection and updating data. The success of the pilot can be attributed to the adapted WHO tools, the team composition in both countries, access to human resources data, and early support of the ministries of health, with the expectation that this methodology can be applied to other country contexts.
An assessment of existing surge capacity of tertiary healthcare system of Khyber Pakhtunkhwa Province of Pakistan using workload indicators for staffing need method
Authors: Haroon Muhammad Zeeshan , Thaver Inayat Hussain 
Published: January 2022

Abstract
Background
Globally the occurrence of disasters has increased more than fourfold during the last three decades. The main concern for the healthcare system responding to a disaster is its ability to deal with the sudden influx of patients and maintaining a certain level of surge capacity. Health workers are considered to be the major driving force behind any health system. Their role gets even more prominent during disasters or public health emergencies. With the lack of information on the health workforce in the tertiary healthcare system of Khyber Pakhtunkhwa, where most of the disaster surge is diverted, it is difficult to plan and respond to accommodate the sudden surge of patients.

Methods
This was a mixed method cross-sectional survey conducted in all the tertiary care hospitals of Khyber Pakhtunkhwa province of Pakistan to assess the current staffing situation and surge capacity based on the current workload. Annual service statistics of 2018 were collected from all the tertiary care hospitals of the province. WISN was piloted with only one healthcare staff category, i.e., for doctors in Ayub Teaching Hospital before assessment in all the tertiary care hospitals was undertaken.

Results
Overall, there were 1215 surplus doctors in medical and allied specialties and 861 doctors in surgical and allied specialties in the tertiary healthcare system. The health care system has an acute shortage of 565 emergency department doctors. The tertiary healthcare system of KP has an overall shortage of 1099 nurses. Based on the WISN generated numbers for doctors, the tertiary care system of KP has a combined healthcare staff (doctors and nurses) that can manage an additional surge of 6.3% of patients with the current patient workload.

Conclusion
The tertiary health care system of the Khyber Pakhtunkhwa Province of Pakistan does not possess the required ≥ 20% HR surge capacity indicating that the tertiary healthcare system is poorly prepared for disasters or public health emergencies. The lack of nursing staff, more than the doctors, is the major reason behind the lack of HR surge capacity of the tertiary health care system.
NAD(P)H: quinone oxidoreductase 1 attenuates oxidative stress and apoptosis by regulating Sirt1 in diabetic nephropathy
Authors: Qiu Duojun , Song Shan , Wang Yuhan , Bian Yawei , Wu Ming , Wu Haijiang , Shi Yonghong , Duan Huijun 
Published: January 2022

Abstract
Background
Diabetic nephropathy (DN) is one of the main complications of diabetes, and oxidative stress plays an important role in its progression. NAD(P)H: quinone oxidoreductase 1 (NQO1) protects cells from oxidative stress and toxic quinone damage. In the present study, we aimed to investigate the protective effects and underlying mechanisms of NQO1 on diabetes-induced renal tubular epithelial cell oxidative stress and apoptosis.

Methods
In vivo, the kidneys of db/db mice, which are a type 2 diabetes model, were infected with adeno-associated virus to induce NQO1 overexpression. In vitro, human renal tubular epithelial cells (HK-2 cells) were transfected with NQO1 pcDNA3.1(+) and cultured in high glucose (HG). Gene and protein expression was assessed by quantitative real-time PCR, western blotting, immunofluorescence analysis, and immunohistochemical staining. Reactive oxygen species (ROS) were examined by MitoSox red and flow cytometry. TUNEL assays were used to measure apoptosis.

Result
In vivo, NQO1 overexpression reduced the urinary albumin/creatinine ratio (UACR) and blood urea nitrogen (BUN) level in db/db mice. Our results revealed that NQO1 overexpression could significantly increase the ratio of NAD+/NADH and silencing information regulator 1 (Sirt1) expression and block tubular oxidative stress and apoptosis in diabetic kidneys. In vitro, NQO1 overexpression reduced the generation of ROS, NADPH oxidase 1 (Nox1) and Nox4, the Bax/Bcl-2 ratio and the expression of Cleaved Caspase-3 and increased NAD+/NADH levels and Sirt1 expression in HK-2 cells under HG conditions. However, these effects were reversed by the Sirt1 inhibitor EX527.

Conclusions
All these data suggest that NQO1 has a protective effect against oxidative stress and apoptosis in DN, which may be mediated by the regulation of Sirt1 through increasing intracellular NAD+/NADH levels. Therefore, NQO1 may be a new therapeutic target for DN.
Cost data in implementation science: categories and approaches to costing
Authors: Gold Heather T. , McDermott Cara , Hoomans Ties , Wagner Todd H. 
Published: January 2022

AbstractA lack of cost information has been cited as a barrier to implementation and a limitation of implementation research. This paper explains how implementation researchers might optimize their measurement and inclusion of costs, building on traditional economic evaluations comparing costs and effectiveness of health interventions. The objective of all economic evaluation is to inform decision-making for resource allocation and to measure costs that reflect opportunity costs—the value of resource inputs in their next best alternative use, which generally vary by decision-maker perspective(s) and time horizon(s). Analyses that examine different perspectives or time horizons must consider cost estimation accuracy, because over longer time horizons, all costs are variable; however, with shorter time horizons and narrower perspectives, one must differentiate the fixed and variable costs, with fixed costs generally excluded from the evaluation. This paper defines relevant costs, identifies sources of cost data, and discusses cost relevance to potential decision-makers contemplating or implementing evidence-based interventions. Costs may come from the healthcare sector, informal healthcare sector, patient, participant or caregiver, and other sectors such as housing, criminal justice, social services, and education. Finally, we define and consider the relevance of costs by phase of implementation and time horizon, including pre-implementation and planning, implementation, intervention, downstream, and adaptation, and through replication, sustainment, de-implementation, or spread.
Osteogenesis Imperfecta: characterization of fractures during pregnancy and post-partum
Authors: Koumakis Eugénie , Cormier-Daire Valérie , Dellal Azeddine , Debernardi Marc , Cortet Bernard , Debiais Françoise , Javier Rose-Marie , Thomas Thierry , Mehsen-Cetre Nadia , Cohen-Solal Martine , Fontanges Elisabeth , Laroche Michel , Porquet-Bordes Valérie , Marcelli Christian , Benachi Alexandra , Briot Karine , Roux Christian , Cormier Catherine 
Published: January 2022

Abstract
Background
Pregnancy and breastfeeding are associated with bone density loss. Fracture occurrence during pregnancy and post-partum, and its determinants, remain poorly known in Osteogenesis Imperfecta (OI). The aim of this study was to characterize fractures that occurred during pregnancy and post-partum in OI patients.

Results
We conducted a retrospective multicentric study including a total of 50 previously pregnant OI women from 10 Bone Centers in France. Among these patients, 12 (24%) patients experienced fractures during pregnancy or in the 6 months following delivery, and 38 (76%) did not experience any fracture. The most frequent localizations were: proximal femur (25%), spine (25%), distal femur (12.5%), and pelvis (12.5%). Fractures during pregnancy occurred during the third trimester and post-partum fractures occurred with a mean delay of 2 months following delivery. No fractures occurred during childbirth.
We next compared the 12 patients with pregnancy or post-partum fractures with the 38 patients without fractures. Mean age at pregnancy was 32.7 ± 3.1 years-old in the fractured group, vs 29.3 ± 5.0 years-old in the non-fractured group (p = 0.002). Breastfeeding was reported in 85.7% of patients in the fractured group, vs 47.1% in the non-fractured group (p = 0.03). All patients with post-partum fractures were breastfeeding. Bone mineral density was significantly lower in patients with pregnancy-related fractures compared with other patients: spine Z-score − 2.9 ± 1.6DS vs − 1.5 ± 1.7DS (p = 0.03), and total hip Z-score − 2.0 ± 0.7DS vs − 0.5 ± 1.4DS (p = 0.04). At least one osteoporosis-inducing risk factor or disease other than OI was identified in 81.8% vs 58.6% of fractured vs non-fractured patients (not significant). Fracture during pregnancy or post-partum was not associated with the severity of OI. Bisphosphonates before pregnancy were reported in 16.7% and 21.1% of patients with pregnancy-related fractures and non-fractured patients, respectively (not significant).

Conclusions
OI management during pregnancy and post-partum should aim for optimal control of modifiable osteoporosis risk factors, particularly in patients with low BMD. Breastfeeding should be avoided.
Dulce Digital-Me: protocol for a randomized controlled trial of an adaptive mHealth intervention for underserved Hispanics with diabetes
Authors: Philis-Tsimikas Athena , Fortmann Addie L. , Godino Job G. , Schultz James , Roesch Scott C. , Gilmer Todd P. , Farcas Emilia , Sandoval Haley , Savin Kimberly L. , Clark Taylor , Chichmarenko Mariya , Jones Jennifer A. , Gallo Linda C. 
Published: January 2022

Abstract
Background
By 2034, the number of US individuals with diabetes is predicted to increase from 23.7 to 44.1 million, and annual diabetes-related spending is expected to grow from $113 to $336 billion. Up to 55% of US Hispanics born in the year 2000 are expected to develop diabetes during their lifetime. Poor healthcare access and cultural barriers prevent optimal care, adherence, and clinical benefit, placing Hispanics at disproportionate risk for costly diabetes complications. Mobile technology is increasingly prevalent in all populations and can circumvent such barriers. Our group developed Dulce Digital, an educational text messaging program that improved glycemic control relative to usual care. Dulce Digital-Me (DD-Me) has been tailored to a participant’s individual needs with a greater focus on health behavior change.

Methods
This is a three-arm, parallel group, randomized trial with equal allocation ratio enrolling Hispanic adults with low income and poorly managed type 2 diabetes (N = 414) from a San Diego County Federally Qualified Health Center. Participants are randomized to receive Dulce Digital, Dulce Digital-Me-Automated, or Dulce Digital-Me-Telephonic. The DD-Me groups include Dulce Digital components plus personalized goal-setting and feedback delivered via algorithm-driven automated text messaging (DD-Me-Automated) or by the care team health coach (DD-Me-Telephonic) over a 12-month follow-up period. The study will examine the comparative effectiveness of the three groups in improving diabetes clinical control [HbA1c, primary outcome; low-density lipoprotein cholesterol (LDL-C), and systolic blood pressure (SBP)] and patient-provider communication and patient adherence (i.e., medication, self-management tasks) over 12 months and will examine cost-effectiveness of the three interventions.

Discussion
Our comparative evaluation of three mHealth approaches will elucidate how technology can be integrated most effectively and efficiently within primary care-based chronic care model approaches to reduce diabetes disparities in Hispanics and will assess two modes of personalized messaging delivery (i.e., automated messaging vs. telephonic by health coach) to inform cost and acceptability.

Trial registration
NCT03130699-All items from the WHO Trial Registration data set are available in https://clinicaltrials.gov/ct2/show/study/NCT03130699.
Efficacy of acupuncture on cognitive function in poststroke depression: study protocol for a randomized, placebo-controlled trial
Authors: Chen Ling , Chen Yi , Wu Lihua , Fu Wen , Wu Luanmian , Fu Wenbin 
Published: January 2022

Abstract
Introduction
Poststroke depression (PSD) is the most common mental complication after stroke and has a serious impact on functional outcomes and quality of life. Antidepressants are the first-line treatment for PSD, but many reported side effects remain. Clinical research has shown that acupuncture has a positive effect on PSD. This trial aims to study the efficacy and safety of acupuncture for PSD and to explore its effect on cognitive function. It is hypothesized that acupuncture treatment improves depressive symptoms, cognitive behavior, and negative emotion processing bias in PSD.

Methods
In this randomized, placebo-controlled, single-blinded trial, fifty-six people with PSD will be randomly allocated into the intervention (n=28) or control (n=28) groups. The intervention group will receive acupuncture treatment, and the control group will receive sham acupuncture treatment, in 20 sessions over 4 weeks. The primary outcome is the change from baseline in the Hamilton Depression Scale-17 (HAMD-17) scores at week 4. Secondary outcomes include the Wisconsin Card Sorting Test (WCST) and latency and amplitude of P1, N170, and P3 of the event-related potentials (ERPs) components to assess the changes in cognitive function and electroencephalography. Outcomes are assessed at baseline and post intervention.

Discussion
Acupuncture therapy could become an alternative treatment for PSD, and it is expected that this trial will provide reliable clinical evidence for the future use of acupuncture for the treatment of PSD.

Trial registration
Chinese Clinical Trial Registry ChiCTR1900026948. Registered on 27 October 2019.
MALDI-TOF mass spectrometry identification of mosquitoes collected in Vietnam
Authors: Huynh Ly Na , Diarra Adama Zan , Nguyen Hong Sang , Tran Long Bien , Do Van Nguyen , Ly Tran Duc Anh , Ho Van Hoang , Nguyen Xuan Quang , Parola Philippe 
Published: January 2022

Abstract
Background
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a tool that has revolutionised clinical microbiology and has recently been described as an innovative and effective approach to arthropod identification.

Methods
In this study, mosquitoes were captured in Vietnam using four different methods (human landing catch, CDC light traps, BG-Sentinel traps, animal-baited net traps). A total of 4215 mosquitoes were captured and morphologically identified as belonging to three genera: Aedes, Anopheles and Culex. We randomly selected 1253 mosquitoes, including 662 specimens of 14 Anopheles species, 200 specimens of two Aedes species and 391 morphologically unidentified Culex specimens, for molecular and MALDI-TOF MS analysis. The DNA from 98 mosquitoes (69 Anopheles specimens, 23 Culex specimens and six Aedes sp. specimens) was subjected to molecular analysis, either to confirm our morphological identification or the MALDI-TOF MS results, as well as to identify the Culex species that were morphologically identified at the genus level and to resolve the discrepancies between the morphological identification and the MALDI-TOF MS identification.

Results
High-quality MS spectra were obtained for 1058 of the 1253 specimens (84%), including 192/200 for Aedes, 589/662 for Anopheles and 277/391 for Culex. The blind test showed that 986/997 (99%) of the specimens were correctly identified by MALDI-TOF MS, with log score values ranging from 1.708 to 2.843. Eleven specimens of Culex could not be identified based on morphological features, MALDI-TOF MS or molecular analysis.

Conclusions
This study enabled us to identify several species of mosquitoes from Vietnam using MALDI-TOF MS, and to enrich our database of MALDI-TOF MS reference spectra.

Graphical Abstract