bluuebunny/crossref_metadata_2025_split huggingface dataset:
Community-based heat-sensitive moxibustion for primary hypertension: study protocol for a randomized controlled trial with patient-preference arms
Authors: Zhou Xu , Li Shuqing , Li Ling , Deng Guihua , Dai Li , Chai Luyu , Wu Qingni , Yao Ziqian , Deng Minchao , Zhu Weifeng , Fu Yong , Sun Xin 
Published: February 2022

Abstract
Background
Low- and middle-income countries have a high prevalence of primary hypertension, but its treatment and control are often low. Heat-sensitive moxibustion (HSM), an innovative acupoint stimulation technique, may be effective for treating hypertension and thus used appropriately in primary healthcare. The objective of this study is to investigate whether HSM is effective and safe for the treatment of primary hypertension in the community.

Methods
This study is a multicenter, pragmatic, randomized controlled trial (RCT) with patient-preference arms. Four hundred patients with primary hypertension from seven communities will be enrolled. Initially, the communities will be randomly assigned into two study clusters, one using compulsory randomization and the other allowing treatment selection by patient preferences. Then, patients in the compulsory randomization cluster will be randomized to receive HSM plus their original antihypertensive regimen (HSM group) or only their original antihypertensive regimen (control group) for 6 months. Patients in the patient preference cluster may choose to receive HSM or control if they have a preference; otherwise, patients will be randomly assigned. The primary outcome is the change in systolic blood pressure from baseline; secondary outcomes include change in diastolic blood pressure, dosage of antihypertensive drugs, quality of life (QoL), severity of hypertensive symptoms, and incidence of cardiovascular events. Patient compliance with the HSM regimen, the cost-effectiveness ratio, and safety outcomes will also be evaluated. Outcome data will be collected at 6 monthly visits.

Discussion
This trial will provide important evidence regarding HSM as a technique for primary hypertension in primary healthcare settings. Given the randomization with patient preferences considered, the trial will also allow analyzing patient-preference effects and the comparison of randomized and nonrandomized samples, to improve the robustness and extrapolation of study conclusions.

Trial registration
ClinicalTrials.govNCT04788563. Registered on March 9, 2021.
A novel homozygous missense variant p.D339N in the PKLR gene correlates with pyruvate kinase deficiency in a Pakistani family: a case report
Authors: Rehman Atta Ur , Rashid Abdur , Hussain Zubair , Shah Khadim 
Published: February 2022

Abstract
Background
Pyruvate kinase deficiency is an exceptionally rare autosomal recessive Mendelian disorder caused by bi-allelic pathogenic variants in the PKLR gene. It is mainly characterized by chronic nonspherocytic hemolytic anemia though other symptoms such as splenomegaly, hepatomegaly, pallor, fatigue, iron overload, shortness of breath, hyperbilirubinemia, and gallstones might also prevail.

Case presentation
We present here a novel genetic defect in the PKLR gene that correlates with pyruvate kinase deficiency phenotype in a consanguineous family from North-Western Pakistan. The family included three affected individuals who were all born to consanguineous parents. The proband, a 13-year-old female of Pashtun ethnicity, showed chronic nonautoimmune hemolytic anemia since birth, extremely low hemoglobin (7.6 g/dL) and pyruvate kinase (12.4 U/g Hb) levels, splenomegaly, and hepatomegaly. Bone marrow aspirate showed a markedly decreased myeloid to erythroid ratio and hypercellular marrow particles due to hyperplasia of the erythroid elements. Molecular characterization of the proband’s genomic DNA uncovered a likely pathogenic homozygous missense variant p.[D339N] in exon 7 of the PKLR gene. In-depth in silico analysis and familial cosegregation implies p.[D339N] as the likely cause of pyruvate kinase deficiency in this family. Further in vitro or in vivo studies are required to validate the impact of p.[D339N] on protein structure and/or stability, and to determine its role in the disease pathophysiology.

Conclusions
In summary, these findings suggest a novel genetic defect in the PKLR gene as a likely cause of pyruvate kinase deficiency, thus further expanding the mutational landscape of this rare Mendelian disorder.
GloMPO (Globally Managed Parallel Optimization): a tool for expensive, black-box optimizations, application to ReaxFF reparameterizations
Authors: Freitas Gustavo Michael , Verstraelen Toon 
Published: February 2022

AbstractIn this work we explore the properties which make many real-life global optimization problems extremely difficult to handle, and some of the common techniques used in literature to address them. We then introduce a general optimization management tool called GloMPO (Globally Managed Parallel Optimization) to help address some of the challenges faced by practitioners. GloMPO manages and shares information between traditional optimization algorithms run in parallel. We hope that GloMPO will be a flexible framework which allows for customization and hybridization of various optimization ideas, while also providing a substitute for human interventions and decisions which are a common feature of optimization processes of hard problems. GloMPO is shown to produce lower minima than traditional optimization approaches on global optimization test functions, the Lennard-Jones cluster problem, and ReaxFF reparameterizations. The novel feature of forced optimizer termination was shown to find better minima than normal optimization. GloMPO is also shown to provide qualitative benefits such a identifying degenerate minima, and providing a standardized interface and workflow manager.
Reproducible untargeted metabolomics workflow for exhaustive MS2 data acquisition of MS1 features
Authors: Yu Miao , Dolios Georgia , Petrick Lauren 
Published: February 2022

AbstractUnknown features in untargeted metabolomics and non-targeted analysis (NTA) are identified using fragment ions from MS/MS spectra to predict the structures of the unknown compounds. The precursor ion selected for fragmentation is commonly performed using data dependent acquisition (DDA) strategies or following statistical analysis using targeted MS/MS approaches. However, the selected precursor ions from DDA only cover a biased subset of the peaks or features found in full scan data. In addition, different statistical analysis can select different precursor ions for MS/MS analysis, which make the post-hoc validation of ions selected following a secondary analysis impossible for precursor ions selected by the original statistical method. Here we propose an automated, exhaustive, statistical model-free workflow: paired mass distance-dependent analysis (PMDDA), for reproducible untargeted mass spectrometry MS2 fragment ion collection of unknown compounds found in MS1 full scan. Our workflow first removes redundant peaks from MS1 data and then exports a list of precursor ions for pseudo-targeted MS/MS analysis on independent peaks. This workflow provides comprehensive coverage of MS2 collection on unknown compounds found in full scan analysis using a “one peak for one compound” workflow without a priori redundant peak information. We compared pseudo-spectra formation and the number of MS2 spectra linked to MS1 data using the PMDDA workflow to that obtained using CAMERA and RAMclustR algorithms. More annotated compounds, molecular networks, and unique MS/MS spectra were found using PMDDA compared with CAMERA and RAMClustR. In addition, PMDDA can generate a preferred ion list for iterative DDA to enhance coverage of compounds when instruments support such functions. Finally, compounds with signals in both positive and negative modes can be identified by the PMDDA workflow, to further reduce redundancies. The whole workflow is fully reproducible as a docker image xcmsrocker with both the original data and the data processing template.
Graphical Abstract
Fruitful exchanges: social networks and food resources amidst change
Authors: Schramski Sam , Barbosa de Lima Ana Carolina 
Published: February 2022

AbstractBackgroundThe Amazon region of Brazil is known both for its significant biological and cultural diversity. It is also a region, like many parts of the country, marked by food insecurity, even amongst its rural agricultural populations. In a novel approach, this paper addresses the networks of exchanges of local food and their relationship to the agrobiodiversity of traditional riverine peoples’ (ribeirinho) households in the Central Amazon. Methodologically, it involves mapping the social networks and affinities between households, inventories of known species, and, finally, statistical tests of the relationships between network and subsequent agrobiodiversity.ResultsThe diversity per area of each land type where food cultivation or management takes place shows how home gardens, fields and orchards are areas of higher diversity and intense cultivation compared to fallow areas. Our findings, however, indicate that a household’s income does appear to be strongly associated with the total agrobiodiversity across cultivation areas. In addition, a household’s agrobiodiversity is significantly associated with the frequency and intensity of food exchanges between households.ConclusionsAgrobiodiversity cannot be considered separate from the breadth of activities focused on sustenance and yields from the cash economy, which riverine people engage in daily. It seems to be connected to quotidian social interactions and exchanges in both predictable and occasionally subtler ways. Those brokers who serve as prominent actors in rural communities may not always be the most productive or in possession of the largest landholdings, although in some cases they are. Their proclivity for cultivating and harvesting a wide diversity of produce may be equally important if not more so.
Synchronous double primary malignancies of the pancreatic body and extrahepatic bile duct treated with pancreatoduodenectomy and splenic artery resection following neoadjuvant chemotherapy with gemcitabine plus nab-paclitaxel: a case report
Authors: Murokawa Takahiro , Okabayashi Takehiro , Sui Kenta , Tabuchi Motoyasu , Iwata Jun 
Published: February 2022

Abstract
Background
Primary pancreatic cancer with synchronous primary tumors in other organs is a rare condition, and its treatment largely depends on the progression of pancreatic cancer. Here, we describe a rare case of double primary malignancies involving borderline resectable pancreatic body and extrahepatic bile duct cancers that were successfully resected after neoadjuvant chemotherapy (NAC), subsequently avoiding total pancreatectomy.

Case presentation
A 61-year-old Japanese male was referred to our hospital by his general practitioner after presenting with elevated liver enzymes during a routine check-up for type 2 diabetes mellitus. He was diagnosed with synchronous borderline resectable pancreatic cancer in the body of the pancreas and lower extrahepatic bile duct cancer with obstructive jaundice. Abdominal computed tomography (CT) confirmed a hypovascular mass in the pancreatic body with partial encasement of the common hepatic artery, left gastric artery, celiac artery, and splenic artery and invasion of the splenic vein. Endoscopic retrograde cholangiopancreatography and bile duct biopsy confirmed lower bile duct cancer. Following multidisciplinary discussion, endoscopic retrograde biliary drainage was performed, and neoadjuvant chemotherapy comprising gemcitabine plus nanoparticle albumin-bound paclitaxel (GEM + nab-PTX) was administered. After a total of seven cycles of chemotherapy, follow-up CT showed that the size of the pancreatic lesion reduced, following which the patient underwent pancreatoduodenectomy with splenic artery resection. The postoperative course was uneventful without any surgical complications or intensive hypoglycemic treatment. The pathological diagnosis was pancreatic ductal adenocarcinoma (ypT3N1aM0 ypStage IIB/UICC 8th) with synchronous extrahepatic cholangiocarcinoma (ypT2N1M0 ypStage IIB/UICC 8th). R0 pancreatic resection was performed with an Evans grade III response to neoadjuvant chemotherapy. The patient was followed up and had no tumor recurrence at 22 months after surgery with adjuvant S-1 chemotherapy, however, died after 32 months after surgery due to multiple liver metastasis and para-aortic lymph node metastasis despite salvage GEM + nab-PTX chemotherapy.

Conclusion
In our case, neoadjuvant chemotherapy for borderline resectable pancreatic cancer and function-preserving pancreatoduodenectomy (R0 resection) for double primary malignancies achieved balanced patient survival and postoperative quality of life.
START-online: acceptability and feasibility of an online intervention for carers of people living with dementia
Authors: Loi Samantha M. , Tropea Joanne , Gaffy Ellen , Panayiotou Anita , Capon Hannah , Chiang Jodi , Bryant Christina , Doyle Colleen , Kelly Michelle , Livingston Gill , Dow Briony 
Published: February 2022

Abstract
Background
With increasing numbers of people living with dementia relying on family to care for them at home, there is an urgent need for practical and evidence-based programs to support carers in maintaining their mental health and well-being. The objective of this study was to evaluate the acceptability and feasibility of a modified STrAtegies for RelaTives (START) program delivered online (START-online).

Method
A mixed-methods non-blinded evaluation of START-online (using Zoom as videoconferencing platform) for acceptability and feasibility (completion rates and qualitative feedback through surveys and focus groups) and quantitative evaluation. This occurred at the National Ageing Research Institute, in metropolitan Victoria, Australia.

Results
Twenty-nine eligible carers were referred, 20 (70%) consented to the study. Of these, 16 (80%) completed all 8 sessions, 2 completed only 3 sessions, and 2 withdrew. Carers’ qualitative feedback indicated that the therapist interaction was valued, content and online delivery of the program was acceptable. Feedback was mixed on the appropriate stage of caring.

Conclusion
START-online was feasible and acceptable for carers, including those living outside of metropolitan areas who might otherwise be unable to access face-to-face programs. With the recent COVID-19 pandemic necessitating social distancing to avoid infection, interventions such as this one have increasing relevance in the provision of flexible services.
Particulate matter-induced hypomethylation of Alu and LINE1 in normal human bronchial epithelial cells and epidermal keratinocytes
Authors: Lee Ji Yun , Lee Won Kee , Kim Dong Sun 
Published: February 2022

Abstract
Background
Airborne particulate matter (PM), a complex mixture of organic and inorganic compounds, is a major public health concern due to its adverse health effects. Understanding the biological action of PM is of particular importance in the improvement of public health. Differential methylation of repetitive elements (RE) by PM might have severe consequences for the structural integrity of the genome and on transcriptional activity, thereby affecting human health. This study aimed to evaluate the effect of inhaled and non-inhaled PM (PM2.5, PM10, and PM10-PAH) exposure on DNA methylation. We quantitatively measured the methylation content of Alu and LINE1 in PM-treated normal human bronchial epithelial cells (NHBE) and normal human epidermal keratinocytes (NHEK) by using whole-genome bisulfite sequencing and pyrosequencing.

Results
All PMs exposure significantly lowered Alu and LINE1 methylation in both cells than in mock-treated controls. Hypomethylation was more prominent in PM10-PAH exposed-NHBE and PM10 exposed-NHEK. Alu and LINE1 methylation change exhibited different sensitivity according to the subfamily evolutionary ages, with stronger effects on the oldest L1-M and Alu J in NHBE, and oldest L1-M and youngest Alu S in NHEK.

Conclusions
These results demonstrate that the differential susceptibility of PM-induced hypomethylation of Alu and LINE1 depends upon RE evolutionary age and PM type.
Staff support in a National Health Service mental health trust in response to the COVID-19 pandemic: qualitative study
Authors: Smith Holly , Zhang Shuo , Jones Abbeygail , Dorrington Sarah , Winter Helen , Beck Alison 
Published: February 2022

BackgroundThe COVID-19 pandemic has highlighted the impact work can have on healthcare workers and the importance of staff support services. Rapid guidance was published to encourage preventive and responsive support for healthcare workers.AimsTo understand mental healthcare staff's help-seeking behaviours and access to support at work in response to the COVID-19 pandemic, to inform iterative improvements to provision of staff support.MethodWe conducted a formative appraisal of access to support and support needs of staff in a National Health Service mental health trust. This involved 11 semi-structured individual interviews using a topic guide. Five virtual staff forums were additional sources of data. Reflexive thematic analysis was used to identify key themes.ResultsPeer-based, within-team support was highly valued and sought after. However, access to support was negatively affected by work pressures, physical distancing and perceived cultural barriers.ConclusionsHealthcare organisations need to help colleagues to support each other by facilitating open, diverse workplace cultures and providing easily accessible, safe and reflective spaces. Future research should evaluate support in the evolving work contexts imposed by COVID-19 to inform interventions that account for differences across healthcare workforces.
Longitudinal trends of "manels" and gender representation at the ASCO Genitourinary Cancers Symposium.
Authors: Huynh Melissa Jessica , Ghosh Anushka , Yeap Beow Y. , Zietman Anthony L. , Vapiwala Neha , Kamran Sophia C. 
Published: February 2022

2 Background: Gender disparity in academic medicine has been a longstanding issue. Efforts have been made to recognize this imbalance and increase inclusivity. Despite this, a recent study examining the prevalence of all-male panels (“manels”) found that female faculty are significantly underrepresented at urology meetings, and nearly two-thirds of the sessions were manels. Therefore, we aimed to investigate the prevalence and longitudinal trends of manels and gender representation across genitourinary oncology disciplines at the ASCO Genitourinary Cancers Symposium (GU ASCO). Methods: GU ASCO online programs from 2018-2021 were used to obtain faculty information. Data collected included perceived gender, medical specialty, and panel role (chair/moderator vs. non-chair/non-moderator). For year 2021, additional data about the panelists, including the number of publications, H-index, citations, and academic rank, was collected. The primary outcomes were the percentage of manels and proportion of female panelists over time. Additionally, female representation among chair/moderators and specialties were evaluated. Results: Among 83 sessions involving 317 faculty members, 227 (71.6%) were males (p<0.001), and 28 panel sessions (33.7%) were manels. Between 2018 and 2020, there was a decrease in the prevalence of manels from 45% to 21.7%, but in 2021, it rose to 32.0%. The proportion of female panel members increased over time from 17.1% in 2018 to 35.7% in 2021 (p=0.012). The role of chair/moderator was predominantly represented by males (67.2%, p<0.001). The proportion of male panelists was particularly high in urology (91.2%, p<0.001) and radiation oncology (81.8%, p=0.002) compared to medical oncology (54.6%). In 2021, male speakers held higher academic rank (i.e. professor, associate, assistant) (p=0.020) and had a greater number of publications (p=0.003), H-index (p=0.009), citations (p=0.014) than females (Table). Conclusions: Over time, the number of female panelists increased with a corresponding decrease in proportion of manels, with the exception of 2021. Future studies that include data on meeting participant demographics will provide insight on whether panelists are over/under-represented in proportion to the audience. While improvements in male and female representation have been made over the years, meeting organizers should strive for representation that reflects a diversity of expertise and perspectives. [Table: see text]
Clinical results of PERICLES: A phase II trial investigating atezolizumab +/- radiotherapy for advanced squamous cell carcinoma of the penis.
Authors: de Vries Hielke Martijn , De Feijter Jeantine , Bekers Elise , Lopez-Yurda Marta , Pos Floris J. , Horenblas Simon , Jordanova Ekatarina S. , Brouwer Oscar R. , Schaake Eva E. , Van Der Heijden Michiel Simon 
Published: February 2022

3 Background: Patients (Pts) with advanced squamous cell carcinoma of the penis (aPeCa) have a poor prognosis (21% 2-year overall survival from moment of diagnosis) and high morbidity, due to progressive locoregional disease. Pre-clinical studies show high rates of infiltrating immune cells and high PD-L1 expression, suggesting that immunotherapy may be beneficial for these patients. In the PERICLES study, we assess the activity of atezolizumab (atezo) in aPeCa pts, with or without radiotherapy (RT) to control locoregional lymph node disease. Methods: A single-centre phase 2 study with two treatment arms (non-randomized) was conducted in 32 histologically confirmed aPeCa pts with a WHO performance status of 0-1 (NCT03686332). Any previous treatment except for immunotherapy was allowed. Study treatment consisted of atezo 1200 mg every 3 weeks (all pts). Pts expected to benefit from RT for locoregional disease control (cohort A) additionally received 33 fractions of 1.5 Gy (locoregional affected lymph node regions and penile region) and 1.8 Gy (macroscopic tumor + margin) irradiation. Response was evaluated with 12-weekly CT scans of the abdomen and thorax using RECIST1.1. Toxicity was scored by NCI-CTCAE V4. The primary endpoint was 1-year progression free survival (PFS) for the full cohort. Results: From Oct 2018 to Aug 2021, 20 pts were included in cohort A (RT + atezo) and 12 pts in cohort B (only atezo). Median follow-up was 22 months (interquartile range (IQR) 4.3-14). Median age was 67 years (IQR 60-72) and all patients had stage IV aPeCa. Pts received no prior treatment (25%), or prior RT (34%), chemoradiation (22%), chemotherapy (6%) or surgery (69%). An immunotherapy or radiotherapy-related grade 3-4 AE was observed in 3/32 (9.4%) and 1/20 (5.0%) patients, respectively. There were no grade 5 treatment-related AEs. One-year PFS was 12% (95% confidence interval (CI) 4.0-33), which did not meet the primary objective. The response rate of RECIST1.1 evaluable pts was 30% (see table). In two patients with pulmonary metastases, a complete response was observed. Initial responses with early progression were seen in 5 pts. Median overall survival (OS) was 12 months (95% CI 5.4-19). Conclusions: Anti-tumor activity of atezo was observed in aPeCa, including complete and durable responses. The trial failed to meet its primary objective (PFS). Our results suggest that a subset of aPeCa pts has incomplete immunological activity and/or early resistance to atezo. Analysis of tumor tissue collected in this trial (including on-treatment biopsies) could suggest new therapeutic strategies to overcome resistance and improve clinical outcome to immunotherapy in aPeCa. Clinical trial information: NCT03686332. [Table: see text]