bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of contralateral breast cancer according to first breast cancer characteristics among women in the USA, 1992–2016
Authors: Ramin Cody , Withrow Diana R. , Davis Lynn Brittny C. , Gierach Gretchen L. , Berrington de González Amy 
Published: February 2021

Abstract
Background
Estimates of contralateral breast cancer (CBC) risk in the modern treatment era by year of diagnosis and characteristics of the first breast cancer are needed to assess the impact of recent advances in breast cancer treatment and inform clinical decision making.

Methods
We examined CBC risk among 419,818 women (age 30–84 years) who were diagnosed with a first unilateral invasive breast cancer and survived ≥ 1 year in the US Surveillance, Epidemiology, and End Results program cancer registries from 1992 to 2015 (follow-up through 2016). CBC was defined as a second invasive breast cancer in the contralateral breast ≥ 12 months after the first breast cancer. We estimated standardized incidence ratios (SIRs) of CBC by year of diagnosis, age at diagnosis, and tumor characteristics for the first breast cancer. Cumulative incidence of CBC was calculated for women diagnosed with a first breast cancer in the recent treatment era (2004–2015, follow-up through 2016).

Results
Over a median follow-up of 8 years (range 1–25 years), 12,986 breast cancer patients developed CBC. Overall, breast cancer patients had approximately twice the risk of developing cancer in the contralateral breast when compared to that expected in the general population (SIR = 2.21, 95% CI = 2.17–2.25). SIRs for CBC declined by year of first diagnosis, irrespective of age at diagnosis and estrogen receptor (ER) status (p-trends < 0.001), but the strongest decline was after an ER-positive tumor. The 5-year cumulative incidence of CBC ranged from 1.01% (95% CI = 0.90–1.14%) in younger women (age < 50 years) with a first ER-positive tumor to 1.89% (95% CI = 1.61–2.21%) in younger women with a first ER-negative tumor.

Conclusion
Declines in CBC risk are consistent with continued advances in breast cancer treatment. The updated estimates of cumulative incidence inform breast cancer patients and clinicians on the risk of CBC and may help guide treatment decisions.
Detection of asymptomatic Leishmania infection in Bangladesh by antibody and antigen diagnostic tools shows an association with post–kala-azar dermal leishmaniasis (PKDL) patients
Authors: Owen Sophie I. , Hossain Faria , Ghosh Prakash , Chowdhury Rajashree , Hossain Md. Sakhawat , Jewell Chris , Cruz Isra , Picado Albert , Mondal Dinesh , Adams Emily R. 
Published: February 2021

Abstract
Background
Asymptomatic Leishmania infections outnumber clinical infections on the Indian subcontinent (ISC), where disease reservoirs are anthroponotic. Diagnostics which detect active asymptomatic infection, which are suitable for monitoring and surveillance, may be of benefit to the visceral leishmaniasis (VL) elimination campaign on the ISC.

Methods
Quantitative polymerase chain reaction (qPCR), loop-mediated isothermal amplification (LAMP), and the direct agglutination test (DAT) were carried out on blood samples, and the Leishmania antigen ELISA was carried out on urine samples collected from 720 household and neighbouring contacts of 276 VL and post–kala-azar dermal leishmaniasis (PKDL) index cases, with no symptoms or history of VL or PKDL, in endemic regions of Bangladesh between September 2016 and March 2018.

Results
Of the 720 contacts of index cases, asymptomatic infection was detected in 69 (9.6%) participants by a combination of qPCR (1.0%), LAMP (2.1%), DAT (3.9%), and Leishmania antigen ELISA (3.3%). Only one (0.1%) participant was detected positive by all four diagnostic tests. Poor agreement between tests was calculated using Cohen’s kappa (κ) statistics; however, the Leishmania antigen ELISA and DAT in combination captured all participants as positive by more than one test. We find evidence for a moderately strong association between the index case being a PKDL case (OR 1.94, p = 0.009), specifically macular PKDL (OR 2.12, p = 0.004), and being positive for at least one of the four tests.

Conclusions
Leishmania antigen ELISA on urine detects active asymptomatic infection, requires a non-invasive sample, and therefore may be of benefit for monitoring transmission and surveillance in an elimination setting in combination with serology. Development of an antigen detection test in a rapid diagnostic test (RDT) format would be of benefit to the elimination campaign.

Graphical Abstract
Microbiota restoration reduces antibiotic-resistant bacteria gut colonization in patients with recurrent Clostridioides difficile infection from the open-label PUNCH CD study
Authors:   for the CDC Prevention Epicenter Program, Langdon Amy , Schwartz Drew J. , Bulow Christopher , Sun Xiaoqing , Hink Tiffany , Reske Kimberly A. , Jones Courtney , Burnham Carey-Ann D. , Dubberke Erik R. , Dantas Gautam 
Published: February 2021

Abstract
Background
Once antibiotic-resistant bacteria become established within the gut microbiota, they can cause infections in the host and be transmitted to other people and the environment. Currently, there are no effective modalities for decreasing or preventing colonization by antibiotic-resistant bacteria. Intestinal microbiota restoration can prevent Clostridioides difficile infection (CDI) recurrences. Another potential application of microbiota restoration is suppression of non-C. difficile multidrug-resistant bacteria and overall decrease in the abundance of antibiotic resistance genes (the resistome) within the gut microbiota. This study characterizes the effects of RBX2660, a microbiota-based investigational therapeutic, on the composition and abundance of the gut microbiota and resistome, as well as multidrug-resistant organism carriage, after delivery to patients suffering from recurrent CDI.

Methods
An open-label, multi-center clinical trial in 11 centers in the USA for the safety and efficacy of RBX2660 on recurrent CDI was conducted. Fecal specimens from 29 of these subjects with recurrent CDI who received either one (N = 16) or two doses of RBX2660 (N = 13) were analyzed secondarily. Stool samples were collected prior to and at intervals up to 6 months post-therapy and analyzed in three ways: (1) 16S rRNA gene sequencing for microbiota taxonomic composition, (2) whole metagenome shotgun sequencing for functional pathways and antibiotic resistome content, and (3) selective and differential bacterial culturing followed by isolate genome sequencing to longitudinally track multidrug-resistant organisms.

Results
Successful prevention of CDI recurrence with RBX2660 correlated with taxonomic convergence of patient microbiota to the donor microbiota as measured by weighted UniFrac distance. RBX2660 dramatically reduced the abundance of antibiotic-resistant Enterobacteriaceae in the 2 months after administration. Fecal antibiotic resistance gene carriage decreased in direct relationship to the degree to which donor microbiota engrafted.

Conclusions
Microbiota-based therapeutics reduce resistance gene abundance and resistant organisms in the recipient gut microbiome. This approach could potentially reduce the risk of infections caused by resistant organisms within the patient and the transfer of resistance genes or pathogens to others.

Trial registration
ClinicalTrials.gov, NCT01925417; registered on August 19, 2013.
Physical activity in Sahara Moroccan hemodialysis patients
Authors: Bahadi A. , Lagtarna H. , Benbria S. , Zajjari Y. , Elkabbaj D. , Zemraoui N. 
Published: February 2021

Abstract
Objective
The evaluation of physical activity for chronic hemodialysis patients is a new approach for patient global care. The objective of this work is to evaluate the physical activity in chronic hemodialysis patients and identify the risk factors associated with reduced physical activity. This is a prospective study for 6 months including 150 chronic hemodialysis patients in the Guelmim-Oued Noun Regionin Moroccan Sahara. We use Baecke's survey, translated and validated in Arabic local language. The socio-demographic, clinical, and biological data were completed during the interrogation and from the medical records of the patients.

Results
The mean age of our patients was 54.6 ± 16.4 years, with male predominance (59%). Most patients have a low education level and 60% were illiterate. Hypertension was found in 54% of our patients, diabetes in 39%, and cardiovascular disease in 10% of patients. Low Physical activity was associated with gender (OR = 4.05), age (OR = 1.03) and high education level (OR = 0.2). Our work has met the various pre-established objectives, however other more specific studies must be conducted to better characterize the profile of physical activity in chronic hemodialysis patients.
Effect of endoscope flexibility on tissue dissection profile assessed with pulsed water jet device: ensuring safety, efficacy, and handling of thin devices for neuroendoscopic surgery
Authors: Kusunoki Tetsuya , Kawaguchi Tomohiro , Nakagawa Atsuhiro , Noguchi Yuta , Osawa Shin-Ichiro , Endo Hidenori , Endo Toshiki , Saito Ryuta , Kanamori Masayuki , Niizuma Kuniyasu , Tominaga Teiji 
Published: February 2021

Abstract
Objective
We developed an actuator-driven pulsed water jet device (ADPJ) for flexible neuroendoscopy to achieve effective tissue dissection with vasculature preservation. Although flexibility is a strong advantage for minimally invasiveness, the effect of the ductile curvature on the dissection profiles remains unknown. The purpose of this study was to clarify the impact of the curvature change of the ADPJ connecting tube on the dissection safety and efficacy.

Results
Three ADPJ connecting tubes with different inner diameters (1.0, 0.75, 0.5 mm) were used to dissect the brain phantom. They were bent at 3 angles: 0°, 60°, and 120°. The dissection profiles were evaluated using the mean depth and coefficient of variation (CV) for efficacy and safety, respectively.The larger inner diameter connecting tube dissected more deeply. The dissection depth was not changed regardless of the curvature degree in each tube. There was no significant difference in CVs regardless of inner diameter and curvature. The ductile curvature of the flexible neuroendoscope did not affect the efficacy and safety of the ADPJ dissection profile. Among the numerous instruments, tube-formed devices, including suction and injecting devices such as ADPJ, can be used safely and effectively without flexibility-related limitations.
Biological characteristics of stem cells derived from burned skin—a comparative study with umbilical cord stem cells
Authors: Dolp Reinhard , Eylert Gertraud , Auger Christopher , Aijaz Ayesha , Chen Yufei Andy , Amini-Nik Saeid , Parousis Alexandra , Datu Andrea-Kaye , Jeschke Marc G. 
Published: February 2021

Abstract
Introduction
Burned human skin, which is routinely excised and discarded, contains viable mesenchymal stromal/stem cells (burn-derived mesenchymal stromal/stem cells; BD-MSCs). These cells show promising potential to enable and aid wound regeneration. However, little is known about their cell characteristics and biological function.

Objectives
This study had two aims: first, to assess critical and cellular characteristics of BD-MSCs and, second, to compare those results with multipotent well-characterized MSCs from Wharton’s jelly of human umbilical cords (umbilical cord mesenchymal stromal/stem cells, UC-MSCs).

Methods
BD- and UC-MSCs were compared using immunophenotyping, multi-lineage differentiation, seahorse analysis for glycolytic and mitochondrial function, immune surface markers, and cell secretion profile assays.

Results
When compared to UC-MSCs, BD-MSCs demonstrated a lower mesenchymal differentiation capacity and altered inflammatory cytokine secretomes at baseline and after stimulation with lipopolysaccharides. No significant differences were found in population doubling time, colony formation, cell proliferation cell cycle, production of reactive oxygen species, glycolytic and mitochondrial function, and in the expression of major histocompatibility complex I and II and toll-like receptor (TLR).

Importance, translation
This study reveals valuable insights about MSCs obtained from burned skin and show comparable cellular characteristics with UC-MSCs, highlighting their potentials in cell therapy and skin regeneration.
Conditioned medium from primary cytotrophoblasts, primary placenta-derived mesenchymal stem cells, or sub-cultured placental tissue promoted HUVEC angiogenesis in vitro
Authors: Ma Haiying , Jiang Shenglu , Du Lili , Liu Jinfang , Xu Xiaoyan , Lu Xiaomei , Ma Ling , Zhu Hua , Wei Jun , Yu Yanqiu 
Published: February 2021

Abstract
Background
As a large capillary network, the human placenta plays an important role throughout pregnancy. Placental vascular development is complex and delicate and involves many types of placental cells, such as trophoblasts, and mesenchymal stem cells. There has been no systematic, comparative study on the roles of these two groups of placental cells and the whole placental tissue in the placental angiogenesis. In this study, primary cytotrophoblasts (CTBs) from early pregnancy and primary human placenta-derived mesenchymal stem cells (hPDMSCs) from different stages of pregnancy were selected as the cell research objects, and full-term placental tissue was selected as the tissue research object to detect the effects of their conditioned medium (CM) on human umbilical vein endothelial cell (HUVEC) angiogenesis.

Methods
We successfully isolated primary hPDMSCs and CTBs, collected CM from these placental cells and sub-cultured placental tissue, and then evaluated the effects of the CM on a series of angiogenic processes in HUVECs in vitro. Furthermore, we measured the levels of angiogenic factors in the CM of placental cells or tissue by an angiogenesis antibody array.

Results
The results showed that not only placental cells but also sub-cultured placental tissue, to some extent, promoted HUVEC angiogenesis in vitro by promoting proliferation, adhesion, migration, invasion, and tube formation. We also found that primary placental cells in early pregnancy, whether CTBs or hPDMSCs, played more significant roles than those in full-term pregnancy. Placental cell-derived CM collected at 24 h or 48 h had the best effect, and sub-cultured placental tissue-derived CM collected at 7 days had the best effect among all the different time points. The semiquantitative angiogenesis antibody array showed that 18 of the 43 angiogenic factors had obvious spots in placental cell-derived CM or sub-cultured placental tissue-derived CM, and the levels of 5 factors (including CXCL-5, GRO, IL-6, IL-8, and MCP-1) were the highest in sub-cultured placental tissue-derived CM.

Conclusions
CM obtained from placental cells (primary CTBs or hPDMSCs) or sub-cultured placental tissue contained proangiogenic factors and promoted HUVEC angiogenesis in vitro. Therefore, our research is helpful to better understand placental angiogenesis regulation and provides theoretical support for the clinical application of placental components, especially sub-cultured placental tissue-derived CM, in vascular tissue engineering and clinical treatments.
Associating the risk of three urinary cancers with obesity and overweight: an overview with evidence mapping of systematic reviews
Authors: Shi Jiyuan , Zhao Liang , Gao Ya , Niu Mingming , Yan Meili , Chen Yamin , Song Ziwei , Ma Xueni , Wang Peng , Tian Jinhui 
Published: February 2021

Abstract
Background
The relationship between cancer with overweight and obesity has been extensively reported. However, the association between urinary cancers with these risk factors remains unclear, with existing reports showing conflicting findings. The current review, therefore, sought to clarify the latter association by assessing the methodological and reporting quality of existing systematic reviews on the subject.

Methods
We first screened PubMed, EMBASE, and Cochrane Library databases for relevant literature and subjected the resulting articles to meta-analysis. We adopted the AMSTAR-2 and PRISMA checklists for assessing methodological and reporting quality, respectively, then performed meta-analyses to determine the relationship between incidence and mortality of three types of urinary cancers with obesity and overweight. Indirect comparisons were also done across subgroups.

Results
All systematic reviews (SRs) were of critically low methodological quality. Seventeen SRs had minimal reporting flaws, and 11 SRs had minor reporting flaws. We found an association between obesity with an incidence of kidney (RR = 1.68, 95% CI 1.47–1.92), bladder (RR = 1.1, 95% CI 1.07–1.13), and prostate (RR = 1.02, 95% CI 0.91, 1.13) cancers. Similarly, overweight was associated with the incidence of the three types of cancer, recording RR values of 1.37 (95% CI 1.26–1.48), 1.07 (95% CI 1.03–1.1), and 1 (95% CI 0.93, 1.07) for kidney, bladder, and prostate cancers, respectively. With regard to the dose analysis, the RR of BMI (per 5 kg/m2 increase) was associated with kidney (RR = 1.24, 95% CI 1.2–1.28), bladder (RR = 1.03, 95% CI 1.02–1.05), and prostate (RR = 1.02, 95% CI 1.01, 1.03) cancers.

Conclusions
This comprehensive quantitative analysis provides an affirmation that overweight and obesity are strong risk factors for kidney cancer, owing to a strong association between them. Conversely, a weak association between overweight and obesity with bladder and prostate cancers confirms their status as mild risk factors for the 2 types of cancer. But due to the low quality of included SRs, the results need to be interpreted with caution.

Systematic review registration
PROSPERO CRD42019119459
Understanding the role of lady health workers in improving access to eye health services in rural Pakistan – findings from a qualitative study
Authors: Bechange Stevens , Schmidt Elena , Ruddock Anna , Khan Itfaq Khaliq , Gillani Munazza , Roca Anne , Nazir Imran , Iqbal Robina , Buttan Sandeep , Bilal Muhammed , Ahmed Leena , Jolley Emma 
Published: February 2021

Abstract
Background
In 1994, the Lady Health Workers (LHWs) Programme was established in Pakistan to increase access to essential primary care services and support health systems at the household and community levels. In Khyber Pakhtunkhwa (KPK) province in northern Pakistan, eye care is among the many unmet needs that LHWs were trained to address, including screening and referral of people with eye conditions to health facilities. However, despite an increase in referrals by LHWs, compliance with referrals in KPK has been very low. We explored the role of LHWs in patient referral and the barriers to patient compliance with referrals.

Methods
Qualitative methodology was adopted. Between April and June 2019, we conducted eight focus group discussions and nine in-depth interviews with 73 participants including patients, LHWs and their supervisors, district managers and other stakeholders. Data were analysed thematically using NVivo software version 12.

Results
LHWs have a broad understanding of basic health care and are responsible for a wide range of activities at the community level. LHWs felt that the training in primary eye care had equipped them with the skills to identify and refer eye patients. However, they reported that access to care was hampered when referred patients reached hospitals, where disorganised services and poor quality of care discouraged uptake of referrals. LHWs felt that this had a negative impact on their credibility and on the trust and respect they received from the community, which, coupled with low eye health awareness, influenced patients’ decisions about whether to comply with a referral. There was a lack of trust in the health care services provided by public sector hospitals. Poverty, deep-rooted gender inequities and transportation were the other reported main drivers of non-adherence to referrals.

Conclusions
Results from this study have shown that the training of LHWs in eye care was well received. However, training alone is not enough and does not result in improved access for patients to specialist services if other parts of the health system are not strengthened. Pathways for referrals should be agreed and explicitly communicated to both the health care providers and the patients.
Modulating gut microbiota in a mouse model of Graves’ orbitopathy and its impact on induced disease
Authors:   and the INDIGO consortium, Moshkelgosha Sajad , Verhasselt Hedda Luise , Masetti Giulia , Covelli Danila , Biscarini Filippo , Horstmann Mareike , Daser Anke , Westendorf Astrid M. , Jesenek Christoph , Philipp Svenja , Diaz-Cano Salvador , Banga J. Paul , Michael Daryn , Plummer Sue , Marchesi Julian R. , Eckstein Anja , Ludgate Marian , Berchner-Pfannschmidt Utta 
Published: February 2021

AbstractBackgroundGraves’ disease (GD) is an autoimmune condition in which autoantibodies to the thyrotropin receptor (TSHR) cause hyperthyroidism. About 50% of GD patients also have Graves’ orbitopathy (GO), an intractable disease in which expansion of the orbital contents causes diplopia, proptosis and even blindness. Murine models of GD/GO, developed in different centres, demonstrated significant variation in gut microbiota composition which correlated with TSHR-induced disease heterogeneity. To investigate whether correlation indicates causation, we modified the gut microbiota to determine whether it has a role in thyroid autoimmunity. Female BALB/c mice were treated with either vancomycin, probiotic bacteria, human fecal material transfer (hFMT) from patients with severe GO or ddH2O from birth to immunization with TSHR-A subunit or beta-galactosidase (βgal; age ~ 6 weeks). Incidence and severity of GD (TSHR autoantibodies, thyroid histology, thyroxine level) and GO (orbital fat and muscle histology), lymphocyte phenotype, cytokine profile and gut microbiota were analysed at sacrifice (~ 22 weeks).ResultsIn ddH2O-TSHR mice, 84% had pathological autoantibodies, 67% elevated thyroxine, 77% hyperplastic thyroids and 70% orbital pathology.Firmicuteswere increased, andBacteroidetesreduced relative to ddH2O-βgal; CCL5 was increased. The random forest algorithm at the genus level predicted vancomycin treatment with 100% accuracy but 74% and 70% for hFMT and probiotic, respectively. Vancomycin significantly reduced gut microbiota richness and diversity compared with all other groups; the incidence and severity of both GD and GO also decreased; reduced orbital pathology correlated positively withAkkermansiaspp. whilst IL-4 levels increased. Mice receiving hFMT initially inherited their GO donors’ microbiota, and the severity of induced GD increased, as did the orbital brown adipose tissue volume in TSHR mice. Furthermore, genusBacteroides, which is reduced in GD patients, was significantly increased by vancomycin but reduced in hFMT-treated mice. Probiotic treatment significantly increased CD25+Treg cells in orbital draining lymph nodes but exacerbated induced autoimmune hyperthyroidism and GO.ConclusionsThese results strongly support a role for the gut microbiota in TSHR-induced disease. Whilst changes to the gut microbiota have a profound effect on quantifiable GD endocrine and immune factors, the impact on GO cellular changes is more nuanced. The findings have translational potential for novel, improved treatments.