bluuebunny/crossref_metadata_2025_split huggingface dataset:
Everyday disease diplomacy: an ethnographic study of diabetes self-care in Vietnam
Authors: Gammeltoft Tine M. , Bùi Thị Huyền Diệu , Vũ Thị Kim Dung , Vũ Đức Anh , Nguyễn Thị Ái , Lê Minh Hiếu 
Published: April 2022

Abstract
Background
Understanding people’s subjective experiences of everyday lives with chronic health conditions such as diabetes is important for appropriate healthcare provisioning and successful self-care. This study explored how individuals with type 2 diabetes in northern Vietnam handle the everyday life work that their disease entails.

Methods
Detailed ethnographic data from 27 extended case studies conducted in northern Vietnam’s Thái Bình province in 2018–2020 were analyzed.

Results
The research showed that living with type 2 diabetes in this rural area of Vietnam involves comprehensive everyday life work. This work often includes efforts to downplay the significance of the disease in the attempt to stay mentally balanced and ensure social integration in family and community. Individuals with diabetes balance between disease attentiveness, keeping the disease in focus, and disease discretion, keeping the disease out of focus, mentally and socially. To capture this socio-emotional balancing act, we propose the term “everyday disease diplomacy.” We show how people’s efforts to exercise careful everyday disease diplomacy poses challenges to disease management.

Conclusions
In northern Vietnam, type 2 diabetes demands daily labour, as people strive to enact appropriate self-care while also seeking to maintain stable social connections to family and community. Health care interventions aiming to enhance diabetes care should therefore combine efforts to improve people’s technical diabetes self-care skills with attention to the lived significance of stable family and community belonging.
Effect of active learning and online discussions on the academic performances of dental students
Authors: Lim Jaeseo , Ko Hyunwoong , Park Jooyong , Ihm Jungjoon 
Published: April 2022

Abstract
Background
COVID-19 caused significant confusion around the world, and dental education was no exception. Therefore, in line with the demands of the times, this study sought to determine the applicability of online active learning to dental education.

Methods
This study was conducted in the second semester of 2020 at a school of dentistry in a selective university in Korea. A total of 114 dental students were recruited. Participants were assigned to four different groups (lecture and discussion [LD], lecture and discussion with instructor’s worksheet [LW], self-study and discussion [SSD], and self-study and discussion with instructor’s worksheet [SW]) using the random breakout room function in the Zoom video conference application. Their final test scores were then analyzed using analysis of variance and the online active learning results were compared with the offline learning results.

Results
The scores were highest for the transfer type items in the SSD group, followed by the SW group and the two lecture groups, which had no significant differences. These scores and pattern differences between the groups were similar for all items. The results suggested that studying by oneself rather than simply listening to lectures enhanced the effects of the discussions and led to higher learning outcomes. In addition, the effect of the instructor's intervention in the middle of the discussion varied depending on the pre-learning activities of discussion. As with previous offline experiments, self-study followed by group discussion had higher learning outcomes for both the verbatim and transfer type items.

Conclusions
In agreement with the Interactive, Constructive, Active, and Passive (ICAP) framework and other active learning theories, the findings clearly indicated that online active learning was applicable to dental students, and when self-study precedes discussion, the learning is richer and the learning outcomes are better.
Engineered Cas12a-Plus nuclease enables gene editing with enhanced activity and specificity
Authors: Huang Hongxin , Huang Guanjie , Tan Zhihong , Hu Yongfei , Shan Lin , Zhou Jiajian , Zhang Xin , Ma Shufeng , Lv Weiqi , Huang Tao , Liu Yuchen , Wang Dong , Zhao Xiaoyang , Lin Ying , Rong Zhili 
Published: April 2022

Abstract
Background
The CRISPR-Cas12a (formerly Cpf1) system is a versatile gene-editing tool with properties distinct from the broadly used Cas9 system. Features such as recognition of T-rich protospacer-adjacent motif (PAM) and generation of sticky breaks, as well as amenability for multiplex editing in a single crRNA and lower off-target nuclease activity, broaden the targeting scope of available tools and enable more accurate genome editing. However, the widespread use of the nuclease for gene editing, especially in clinical applications, is hindered by insufficient activity and specificity despite previous efforts to improve the system. Currently reported Cas12a variants achieve high activity with a compromise of specificity. Here, we used structure-guided protein engineering to improve both editing efficiency and targeting accuracy of Acidaminococcus sp. Cas12a (AsCas12a) and Lachnospiraceae bacterium Cas12a (LbCas12a).

Results
We created new AsCas12a variant termed “AsCas12a-Plus” with increased activity (1.5~2.0-fold improvement) and specificity (reducing off-targets from 29 to 23 and specificity index increased from 92% to 94% with 33 sgRNAs), and this property was retained in multiplex editing and transcriptional activation. When used to disrupt the oncogenic BRAFV600E mutant, AsCas12a-Plus showed less off-target activity while maintaining comparable editing efficiency and BRAFV600E cancer cell killing. By introducing the corresponding substitutions into LbCas12a, we also generated LbCas12a-Plus (activity improved ~1.1-fold and off-targets decreased from 20 to 12 while specificity index increased from 78% to 89% with 15 sgRNAs), suggesting this strategy may be generally applicable across Cas12a orthologs. We compared Cas12a-Plus, other variants described in this study, and the reported enCas12a-HF, enCas12a, and Cas12a-ultra, and found that Cas12a-Plus outperformed other variants with a good balance for enhanced activity and improved specificity.

Conclusions
Our discoveries provide alternative AsCas12a and LbCas12a variants with high specificity and activity, which expand the gene-editing toolbox and can be more suitable for clinical applications.
Time spent in outdoor light is associated with the risk of dementia: a prospective cohort study of 362094 participants
Authors: Ma Ling-Zhi , Ma Ya-Hui , Ou Ya-Nan , Chen Shi-Dong , Yang Liu , Dong Qiang , Cheng Wei , Tan Lan , Yu Jin-Tai 
Published: April 2022

Abstract
Background
Data on the association between free-living daytime sunlight exposure and incident dementia are scarce. The objective is to evaluate whether the time spent in outdoor light is related to the dementia risk and to investigate whether the optimal duration varies with clinical parameters.

Methods
Data were from a prospective cohort of 362,094 UK Biobank participants. A questionnaire survey was conducted to investigate how many hours the participants spent outdoors on typical summer and winter days. A restricted cubic spline (RCS) was performed to explore the potential nonlinear relationship between sunlight exposure and the risk of dementia. We used multivariate Cox proportional hazard regression models to estimate the hazard ratios (HRs) for the associations between sunlight exposure and dementia outcomes, with the change points as a reference.

Results
After a median follow-up of 9.0 years, 4149 (1.15%) individuals were diagnosed with dementia. RCS showed a J-shaped relationship between time spent in outdoor light and the dementia risk, with the lowest risk at three change points (1.5 h/day on average, 2 h/day in summer, and 1 h/day in winter). Cox hazard regression models showed a marked increase in risk at low exposure (HR=1.287, 95%CI 1.094–1.515) but a relatively slow increase at higher exposure (HR=1.070, 95%CI 1.031–1.10). Results are more pronounced among participants over 60 years old, females, and those with exactly 7 h of sleep every night.

Conclusions
Sunlight exposure had a J-shaped association with dementia risk. Giving detailed guidance on sunlight exposure can effectively prevent dementia.
Clinically actionable cancer somatic variants (CACSV): a tumor interpreted dataset for analytical workflows
Authors: Sobahy Turki M. , Tashkandi Ghassan , Bahussain Donya , Al-Harbi Raneem 
Published: April 2022

Abstract
Background
The recent development and enormous application of parallel sequencing technology in oncology has produced immense amounts of cell-specific genetic information. However, publicly available cell-specific genetic variants are not explained by well-established guidelines. Additionally, cell-specific variants interpretation and classification has remained a challenging task and lacks standardization. The Association for Molecular Pathology (AMP), the American Society of Clinical Oncology (ASCO), and the College of American Pathologists (CAP) published the first consensus guidelines for cell-specific variants cataloging and clinical annotations.

Methods
AMP–ASCO–CAP recommended sources and information were downloaded and used as follows: relative knowledge in oncology clinical practice guidelines; approved, investigative or preclinical drugs; supporting literature and each gene-tumor site correlation. All information was homogenized into a single knowledgebase. Finally, we incorporated the consensus recommendations into a new computational method.

Results
A subset of cancer genetic variants was manually curated to benchmark our method and well-known computational algorithms. We applied the new method on freely available tumor-specific databases to produce a clinically actionable cancer somatic variants (CACSV) dataset in an easy-to-integrate format for most clinical analytical workflows. The research also showed the current challenges and limitations of using different classification systems or computational methods.

Conclusion
CACSV is a step toward cell-specific genetic variants standardized interpretation as it is readily adaptable by most clinical laboratory pipelines for somatic variants clinical annotations. CACSV is freely accessible at (https://github.com/tsobahytm/CACSV/tree/main/dataset).
Angiopoietin2-mediated caveolin1 phosphorylation regulating transcytosis of renal tubular epithelial cell contributes to the occurrence of albuminuria under high glucose exposure
Authors: Liu Jing , Yao Junxia , Zhao Yi , Su Jinxuan , Ye Jiajia , Wang Yumei 
Published: April 2022

Abstract
Background
Microlbuminuria is the earliest clinical evidence of diabetic kidney disease (DKD) and contributes to the induction and/or progression of DKD. Previous studies have shown that increased expression of angiopoietin2 (ANGPT2) is correlated with an increase in albuminuria. However, the critical role of ANGPT2 in albuminuria development remains unclear. Some studies have shown the significance of transcytosis in the occurrence of albuminuria, but it is unknown whether it takes place in albumin recycling in renal tubular cells of patients with DKD. Furthermore, the potential mechanism of this association also remains unclear.

Methods
In this study, human renal tubular epithelial cells (HK-2) were cultured with high glucose in a Transwell plate to establish a transcytosis model, while C57BL/6 mice were intraperitoneally injected with streptozotocin to establish a DKD model. The expression of ANGPT2 and caveolin1 (CAV1) phosphorylation was dectected through immunohistochemistry and western blot analysis.

Results
Transcytosis of albumin in renal tubular epithelial cells was downregulated after high glucose exposure, and increased expression of ANGPT2 and CAV1 phosphorylation both in vivo and in vitro was observed. Inhibition of ANGPT2 and CAV1 independently promoted transcytosis. Furthermore, ANGPT2 downregulation inhibited CAV1 phosphorylation, whereas CAV1 phosphorylation had no effect on the expression of ANGPT2.

Conclusions
ANGPT2 reduces albumin transcytosis across renal tubular epithelial cells under high glucose conditions by activating CAV1 phosphorylation, thus increasing albuminuria in DKD. These findings suggested that ANGPT2 and CAV1 may be promising therapeutic targets for albuminuria in DKD.
Timing of pharmacologic venous thromboembolism prophylaxis initiation for trauma patients with nonoperatively managed blunt abdominal solid organ injury: a systematic review and meta-analysis
Authors: Lamb Tyler , Lenet Tori , Zahrai Amin , Shaw Joseph R. , McLarty Ryan , Shorr Risa , Le Gal Grégoire , Glen Peter 
Published: April 2022

AbstractBackgroundBlunt abdominal solid organ injury is common and is often managed nonoperatively. Clinicians must balance risk of both hemorrhage and thrombosis. The optimal timing of pharmacologic venous thromboembolism prophylaxis (VTEp) initiation in this population is unclear. The objective was to evaluate early (< 48 h) compared to late initiation of VTEp in adult trauma patients with blunt abdominal solid organ injury managed nonoperatively.MethodsEmbase, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched from inception to March 2021. Studies comparing timeframes of VTEp initiation were considered. The primary outcome was failure of nonoperative management (NOM) after VTEp initiation. Secondary outcomes included risk of transfusion, other bleeding complications, risk of deep vein thrombosis (DVT) and pulmonary embolism, and mortality.ResultsTen cohort studies met inclusion criteria, with a total of 4642 patients. Meta-analysis revealed a statistically significant increase in the risk of failure of NOM among patients receiving early VTEp (OR 1.76, 95% CI 1.01–3.05,p = 0.05). There was no significant difference in risk of transfusion. Odds of DVT were significantly lower in the early group (OR 0.36, 95% CI 0.22–0.59,p < 0.0001). There was no difference in mortality (OR 1.50, 95% CI 0.82–2.75,p = 0.19). All studies were at serious risk of bias due to confounding.ConclusionsInitiation of VTEp earlier than 48 h following hospitalization is associated with an increased risk of failure of NOM but a decreased risk of DVT. Absolute failure rates of NOM are low. Initiation of VTEp at 48 h may balance the risks of bleeding and VTE.
Squamous cell carcinoma of the lung presenting as a fungating ulcerated skin lesion: a case report
Authors: Chisenga Rose , Adenwala Tasneem , Kim William , Mujuni Daniel , Samuel Rachel 
Published: April 2022

Abstract
Background
Our patient presents with a novel presentation of a fungated ulcerated skin lesion as the initial presentation of lung cancer. The literature describes skin metastases from lung cancer as nodular, papular, and zosteriform. Our case is a fungating ulcerated skin lesion which is not widely reported in literature. There is a still a need for more data on the clinical presentation and prognosis of such cases as it will elucidate the diagnostic challenges and treatment management.

Case presentation
We present a case of a 55 year old Caucasian male with a 60-pack-year smoking history initially presenting with a nodule on his right upper back that quickly fungated and ulcerated requiring surgical excision. Biopsy of both the skin lesion and the lung mass confirmed squamous cell carcinoma (SCC) and the lung mass being the primary tumor. The patient’s clinical and functional status severely declined during his hospital stay and was later discharged to hospice without therapeutic intervention. He later expired a month after hospice stay.

Conclusions
Although uncommon, this case clearly illustrates that skin metastases can be the initial finding of primary lung cancer and that not all patients with lung cancer will present with bronchopulmonary symptoms. It also illustrates that a fungating ulcerated lesion can be the initial presentation of lung cancer in addition to nodular, papular, and zosteriform presentations noted in the literature.
Global status of antimicrobial resistance among environmental isolates of Vibrio cholerae O1/O139: a systematic review and meta-analysis
Authors: Yuan Xin-hui , Li Yu-mei , Vaziri Ali Zaman , Kaviar Vahab Hassan , Jin Yang , Jin Yu , Maleki Abbas , Omidi Nazanin , Kouhsari Ebrahim 
Published: April 2022

Abstract
Background
Vibrio cholerae O1/O139 were the predominant circulating serogroups exhibiting multi-drug resistance (MDR) during the cholera outbreak which led to cholera treatment failures.

Objective
This meta-analysis aimed to evaluate the weighted pooled resistance (WPR) rates in V. cholerae O1/O139 isolates obtained from environmental samples.

Methods
We systematically searched the articles in PubMed, Scopus, and Embase (until January 2020). Subgroup analyses were then employed by publication year, geographic areas, and the quality of studies. Statistical analyses were conducted using STATA software (ver. 14.0).

Results
A total of 20 studies investigating 648 environmental V. cholerae O1/O139 isolates were analysed. The majority of the studies were originated from Asia (n = 9). In addition, a large number of studies (n = 15 i.e. 71.4%) included in the meta-analysis revealed the resistance to cotrimoxazole and ciprofloxacin. The WPR rates were as follows: cotrimoxazole 59%, erythromycin 28%, tetracycline 14%, doxycycline 5%, and ciprofloxacin 0%. There was increased resistance to nalidixic acid, cotrimoxazole, furazolidone, and tetracycline while a decreased resistance to amoxicillin, ciprofloxacin, erythromycin, chloramphenicol, ampicillin, streptomycin, and ceftriaxone was observed during the years 2000–2020. A significant decrease in the doxycycline and ciprofloxacin-resistance rates in V. cholerae O1/O139 isolates was reported over the years 2011–2020 which represents a decrease in 2001–2010 (p < 0.05).

Conclusions
Fluoroquinolones, gentamicin, ceftriaxone, doxycycline, kanamycin, and cefotaxime showed the highest effectiveness and the lowest resistance rate. However, the main interest is the rise of antimicrobial resistance in V. cholerae strains especially in low-income countries or endemic areas, and therefore, continuous surveillance, careful appropriate AST, and limitation on improper antibiotic usage are crucial.
Viral haemorrhagic fevers and malaria co-infections among febrile patients seeking health care in Tanzania
Authors: Rugarabamu Sima , Rumisha Susan F. , Mwanyika Gaspary O. , Sindato Calvin , Lim Hee-Young , Misinzo Gerald , Mboera Leonard E. G. 
Published: April 2022

Abstract
Background
In recent years there have been reports of viral haemorrhagic fever (VHF) epidemics in sub-Saharan Africa where malaria is endemic. VHF and malaria have overlapping clinical presentations making differential diagnosis a challenge. The objective of this study was to determine the prevalence of selected zoonotic VHFs and malaria co-infections among febrile patients seeking health care in Tanzania.

Methods
This facility-based cross-sectional study was carried out between June and November 2018 in Buhigwe, Kalambo, Kyela, Kilindi, Kinondoni, Kondoa, Mvomero, and Ukerewe districts in Tanzania. The study involved febrile patients seeking health care from primary healthcare facilities. Blood samples were collected and tested for infections due to malaria, Crimean-Congo haemorrhagic fever (CCHF), Ebola virus disease (EVD), Marburg virus disease (MVD), Rift Valley fever (RVF) and yellow fever (YF). Malaria infections were tested using rapid diagnostics tests while exposure to VHFs was determined by screening for immunoglobulin M antibodies using commercial enzyme-linked immunosorbent assays. The Chi-square test was used to compare the proportions.

Results
A total of 308 participants (mean age = 35 ± 19 years) were involved in the study. Of these, 54 (17.5%) had malaria infection and 15 (4.8%) were positive for IgM antibodies against VHFs (RVF = 8; CCHF = 2; EBV = 3; MBV = 1; YF = 1). Six (1.9%) individuals had both VHF (RVF = 2; CCHF = 1; EVD = 2; MVD = 1) and malaria infections. The highest co-infection prevalence (0.6%) was observed among individuals aged 46‒60 years (P < 0.05). District was significantly associated with co-infection (P < 0.05) with the highest prevalence recorded in Buhigwe (1.2%) followed by Kinondoni (0.9%) districts. Headache (100%) and muscle, bone, back and joint pains (83.3%) were the most significant complaints among those infected with both VHFs and malaria (P = 0.001).

Conclusions
Co-infections of VHF and malaria are prevalent in Tanzania and affect more the older than the younger population. Since the overlapping symptoms in co-infected individuals may challenge accurate diagnosis, adequate laboratory diagnosis should be emphasized in the management of febrile illnesses.
Polymorphisms of potential drug resistant molecular markers in Plasmodium vivax from China–Myanmar border during 2008‒2017
Authors: Wang Zhensheng , Wei Chunyan , Pan Yunchun , Wang Zhihua , Ji Xin , Chen Qianqian , Zhang Lianhui , Wang Zenglei , Wang Heng 
Published: April 2022

Abstract
Background
Plasmodium vivax remains the predominant species at the China–Myanmar border, imposing a major challenge to the recent gains in regional malaria elimination. To closely supervise the emerging of drug resistance in this area, we surveyed the variations in genes potentially correlated with drug resistance in P. vivax parasite and the possible drug selection with time.

Methods
A total of 235 P. vivax samples were collected from patients suffering uncomplicated malaria at Yingjiang, Tengchong, and Longling counties, and Nabang port in China, Yunnan province, and Laiza sub-township in Myanmar, from 2008 to 2017. Five potential drug resistance genes were amplified utilizing nested-PCR and analyzed, including pvdhfr, pvdhps, pvmdr1, pvcrt-o, and pvk12. The Pearson’s Chi-squared test or Fisher’s exact test were applied to determine the statistical frequency differences of mutations between categorical data.

Results
The pvdhfr F57I/L, S58R, T61M and S117T/N presented in 40.6%, 56.7%, 40.1%, and 56.0% of the sequenced P. vivax isolates, and these mutations significantly decreased with years. The haplotype formed by these quadruple mutations predominated in Yingjiang, Tengchong, Longling and Nabang. While a mutation H99S/R (56.6%) dominated in Laiza and increased with time. In pvdhps, the A383G prevailed in 69.2% of the samples, which remained the most prevalent haplotype. However, a significant decrease of its occurrence was also noticed over the time. The S382A/C and A553G existed in 8.4% and 30.8% of the isolates, respectively. In pvmdr1, the mutation Y976F occurred at a low frequency in 5/232 (2.2%), while T958M was fixed and F1076L was approaching fixed (72.4%). The K10 insertion was detected at an occurrence of 33.2% in pvcrt-o, whereas there was no significant difference among the sites or over the time. No mutation was identified in pvk12.

Conclusions
Mutations related with resistance to antifolate drugs are prevalent in this area, while their frequencies decrease significantly with time, suggestive of increased susceptibility of P. vivax parasite to antifolate drugs. Resistance to chloroquine (CQ) is possibly emerging. However, since the molecular mechanisms underneath CQ resistance is yet to be better understood, close supervision of clinical drug efficiency and continuous function investigation is urgently needed to alarm drug resistance.

Graphical abstract