bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detecting gene–gene interactions from GWAS using diffusion kernel principal components
Authors: Walakira Andrew , Ocira Junior , Duroux Diane , Fouladi Ramouna , Moškon Miha , Rozman Damjana , Van Steen Kristel 
Published: February 2022

AbstractGenes and gene products do not function in isolation but as components of complex networks of macromolecules through physical or biochemical interactions. Dependencies of gene mutations on genetic background (i.e., epistasis) are believed to play a role in understanding molecular underpinnings of complex diseases such as inflammatory bowel disease (IBD). However, the process of identifying such interactions is complex due to for instance the curse of high dimensionality, dependencies in the data and non-linearity. Here, we propose a novel approach for robust and computationally efficient epistasis detection. We do so by first reducing dimensionality, per gene via diffusion kernel principal components (kpc). Subsequently, kpc gene summaries are used for downstream analysis including the construction of a gene-based epistasis network. We show that our approach is not only able to recover known IBD associated genes but also additional genes of interest linked to this difficult gastrointestinal disease.
Effect of topical local anaesthesia on injection pain associated with administration of sterile water injections - a randomized controlled trial
Authors: Mårtensson Lena B. , Gunnarsson Britt-Marie , Karlsson Sandra , Lee Nigel , Bergh Ingrid 
Published: February 2022

Abstract
Background
Sterile water injections can provide effective pain relief during childbirth, particularly for low back pain related to childbirth. However, the pain associated administering the injections can negatively impact women’s impressions of the procedure. It may discourage women from considering repeat doses despite the quality of analgesia experienced. Determining strategies to reduce the pain related to the administration of sterile water injections would improve the acceptability of the technique. Therefore, the aim of this study was to evaluate the effect of topical local anesthesia on the pain associated with administration of sterile water injections.

Methods
The study was designed as a multi-arm single-blind, randomized, controlled trial and 120 female healthy students were randomly divided according to one of four groups. The Intervention group received sterile water injections with topical local anesthesia. Control group 1 received sterile water injections without topical local anesthesia, control group 2 received injections of isotonic saline 0.9% with topical local anesthesia and control group 3 received injections of isotonic saline 0.9% without topical local anesthesia. Pain Immediately after the injections and subsidence in pain were recorded using a visual analogue scale. Sensations in the injection area were reported 15 min and the day after the injections.

Results
The main finding of this study was that local anesthesia with EMLA® reduces the pain associated with the administration of intracutaneous sterile water injections. There was a significant difference in the self-assessed pain score immediately following the injections between the control (73.3 mm) and intervention groups (50.0 mm), p = 0.001. No adverse side effects were reported.

Conclusion
Local anesthesia with EMLA® reduces the pain associated with intracutaneous administration of sterile water injections.

Trial registration
The study was registered 08/07/2014 at ClinicalTrials.gov Identifier: NCT02213185.
Influenza circulating viruses, positivity rate and risk factors for influenza associated severe acute respiratory infection during 2018/2019 winter season, Yemen
Authors: Al Amad Mohammed , Almoayed Khaled 
Published: February 2022

Abstract
Background
The burden of seasonal influenza in conflict counties is exacerbated due to limited resource and collapse of health system. During 2018 /2019 season, two-fold increase in the incidence of influenza was reported in Yemen with 22% case fatality of severe acute respiratory infection (SARI). The aims are to analyze the influenza circulating viruses, positivity rate and risk factors for hospitalizing influenza associated-SARI.

Methodology
We used a retrospective analytical study based on surveillance data. All reported patients during 2018/2019 season, fulfilling the WHO cases definition for SARI or influenza like illness (ILI), and had laboratory result from the National Laboratory were included. Influenza positivity rate was calculated, all SARI and ILI patients with positive influenza were included for further analysis by univariate and multivariate binary logistic regression. Crude and adjusted Odds ratio (AOR), 95% confidence interval and P-value < 0.05 were used for statistically significant.

Results
Out of 2186 patients enrolled, 768 patients were tested for influenza viruses,: 19% were children < 15 years, 15% were ≥ 65 years, 69% males and 18% had co-morbidity with chronic diseases. Patients with SARI were 37% and 63% were ILI patients. Influenza viruses were detected in 411 (53.5%), 68% were influenza A subtype (H1N1)pdm09, 27% influenza B and 5% was influenza A not subtyped. The influenza positivity was significantly higher in SARI compared to ILI for patients < 15 years (95% vs, 66%, p < 0.001), and patients ≥ 65 years (83% vs. 56%, p < 0.002), respectively. The highest positivity for influenza type A and B reached 44% and 33% for patients ≥ 65 years and < 15 years, respectively. The risk factors for influenza-associated SARI in multivariate analysis included age < 5 [AOR 2.8] and ≥ 65 years old [AOR 3.1] compared to age 5– < 25 years, diabetes [AOR 4.7], heart diseases [AOR 3.1] and chronic respiratory diseases [AOR 5.0].

Conclusion
The influenza positivity during 2018/2019 winter season was high in Yemen and varied by age distribution. Influenza subtype A (H1N1) pdm09 was the predominant and co circulated with influenza B. An influenza vaccination program for the risk group is necessary. Strengthening lab capacity to detect respiratory pathogens and further prospective study for more comprehensive picture are recommended.
Relationship between the appropriateness of antibiotic treatment and clinical outcomes/medical costs of patients with community-acquired acute pyelonephritis: a multicenter prospective cohort study
Authors: Yoon Choseok , Park Se Yoon , Kim Bongyoung , Kwon Ki Tae , Ryu Seong-yeol , Wie Seong-Heon , Jo Hyun-uk , Kim Jieun , Hong Kyung-Wook , Kim Hye In , Kim Hyun ah , Kim Mi-Hee , Bae Mi-Hyun , Sohn Yong-Hak , Kim Jieun , Lee Yangsoon , Pai Hyunjoo 
Published: February 2022

Abstract
Background
Inappropriate use of antibiotics not only increases antibiotic resistance as collateral damage but also increases clinical failure rates and medical costs. The purpose of this study was to determine the relationship between the appropriateness of antibiotic prescription and outcomes of community-acquired acute pyelonephritis (CA-APN).

Methods
A multicenter prospective cohort study was conducted at eight hospitals in Korea between September 2017 and August 2018. All hospitalized patients aged ≥ 19 years who were diagnosed with CA-APN on admission were recruited. The appropriateness of empirical and definitive antibiotics, as well as the appropriateness of antibiotic treatment duration and route of administration, was evaluated in accordance with the guideline and expert opinions. Clinical outcomes and medical costs were compared between patients who were administered antibiotics ‘appropriately’ and ‘inappropriately.’

Results
A total of 397 and 318 patients were eligible for the analysis of the appropriateness of empirical and definitive antibiotics, respectively. Of them, 10 (2.5%) and 18 (5.7%) were administered ‘inappropriately’ empirical and definitive antibiotics, respectively. Of the 119 patients whose use of both empirical and definitive antibiotics was classified as ‘optimal,’ 57 (47.9%) received antibiotics over a longer duration than that recommended; 67 (56.3%) did not change to oral antibiotics on day 7 of hospitalization, even after stabilization of the clinical symptoms. Patients who were administered empirical antibiotics ‘appropriately’ had shorter hospitalization days (8 vs. 10 days, P = 0.001) and lower medical costs (2381.9 vs. 3235.9 USD, P = 0.002) than those who were administered them ‘inappropriately.’ Similar findings were observed for patients administered both empirical and definitive antibiotics ‘appropriately’ and those administered either empirical or definitive antibiotics ‘inappropriately’.

Conclusions
Appropriate use of antibiotics leads to better outcomes, including reduced hospitalization duration and medical costs.
Randomized double-blind clinical trial comparing safety and efficacy of the biosimilar BCD-021 with reference bevacizumab
Authors: Stroyakovskiy Daniil L. , Fadeeva Natalya V. , Matrosova Marina P. , Shelepen Konstantin G. , Adamchuk Grigoriy A. , Roy Bodhisatta , Nagarkar Rajnish , Kalloli Mahesh , Zhuravleva Daria , Voevodin Georgiy D. , Shustova Mariya S. , Kryukov Fedor 
Published: February 2022

Abstract
Background
BCD-021 is a bevacizumab biosimilar which was shown to be equivalent to reference bevacizumab in a wide panel of physicochemical studies as well as preclinical studies in vitro and in vivo. International multicenter phase III clinical trial was conducted to compare efficacy and safety of BCD-021 and reference bevacizumab in combination with paclitaxel and carboplatin in a first-line treatment of inoperable or advanced non-squamous non-small-cell lung cancer (NSCLC).

Methods
Patients with no previous treatment for advanced non-squamous NSCLC were randomly assigned 3:2 to BCD-021 or reference bevacizumab and were treated with bevacizumab + paclitaxel + carboplatin. Therapy continued for 6 cycles (every 3 weeks), until progression of the disease or unbearable toxicity. The primary study endpoint was the overall response rate. The study goal was to prove the equivalent efficacy of BCD-021 and reference bevacizumab. Equivalence margins for 95% CI for the difference in the overall response rates were set at [-18%; 18%], for 90% CI for the ratio of overall response rate were set at [67%; 150%].

Results
In total 357 patients were enrolled in the study, 212 in the BCD-021 group and 145 in the reference bevacizumab group. The ORR was 34.63% in the BCD-022 group and 33.82% in the reference bevacizumab group. Limits of 95% CI for the difference in overall response rates between the groups were [-9.47%; 11.09%]. Limits of 90% CI for the ratio of overall response rate between the groups were [79.6%; 131.73%]. For both approaches CI lied within predetermined equivalence margins. Profile of adverse events (AEs) was similar between the groups (any AEs were reported in 86.89% of patients in BCD-021 group and 89.05% of patients in reference group). No unexpected adverse reactions were reported throughout the study. No statistically significant differences regarding anti-drug antibody occurrence rate was found between BCD-022 (n=4; 1.96%) and comparator (n=5; 3.65%). Both drug products showed low occurrence rate and short life of anti-bevacizumab antibodies. Pharmacokinetics assessment after 1st and 6th study drug injection also demonstrated equivalent PK parameters by all outcome measures.

Conclusions
Thus, the results of this study demonstrated therapeutic equivalence of bevacizumab biosimilar BCD-021 and referent bevacizumab drug.

Trial registration
The trial was registered with ClinicalTrials.gov (Study Number NCT01763645, date of registration 09/01/2013).
Sociodemographic and socioeconomic correlates of learning disability in preterm children in the United States
Authors: Okoli Menkeoma Laura , Ogbu Chukwuemeka E. , Enyi Chioma O. , Okoli Ibuchim C. , Wilson Ronee E. , Kirby Russell S. 
Published: February 2022

Abstract
Background
In 2019, 1 in every 10 infants born in the United States was preterm. Prematurity has life-threatening consequences and causes a range of developmental disabilities, of which learning disability is a prevalent complication. Despite the availability of special services for children living with learning disability, gaps still exist in terms of access due to socioeconomic factors. The aim of this study is to evaluate socioeconomic and sociodemographic correlates of learning disability in preterm children.

Methods
This cross-sectional study used data from the 2016–2018 National Survey of Children’s Health. Weighted multivariable analyses were conducted to ascertain the association of sociodemographic and socioeconomic factors on learning disability among preterm children. The main outcome variable was the presence of learning disability.

Results
Among 9555 preterm children in our study population, 1167 (12%) had learning disability. Learning disability was significantly associated with health insurance, food situation, and poverty level after adjustment for other variables. Children currently insured had lower odds of having learning disability compared to those without health insurance (OR = 0.79, 95% C.I. = 0.70–0.91). Also, children living in households that cannot afford nutritious meals are more likely to have learning disability compared to those that can afford nutritious meals at home (OR = 1.55, 95% C.I. = 1.22–1.97).

Conclusion
These findings highlight the need for intervention efforts to target these children living with a learning disability to achieve the 2004 Individuals with Disabilities Education Act of promoting educational equality and empowerment of children living with a learning disability.
Improvised use of a digital tool for social interaction in a Norwegian care facility during the COVID-19 pandemic: an exploratory study
Authors: Badawy Abeer , Solberg Mads , Obstfelder Aud Uhlen , Alnes Rigmor Einang 
Published: February 2022

Abstract
Background
Digital tools for social communication have been deployed in care facilities during the COVID-19 pandemic to facilitate social connectedness between older people and their next of kin in a safe manner. This study explores how and why health care professionals facilitate the ad hoc and prompt use of a technology for social communication, known as KOMP, in care facilities in western Norway to promote communication and social engagement among residents and their next of kin during the crisis.

Methods
To investigate the perspectives and practices of health care professionals, we conducted focus groups, individual interviews, and participant observation in public short- and long-term care facilities in western Norway. An explorative investigation with inductive content analysis was applied to analyse interview transcripts and fieldnotes from participant observation.

Results
The resulting qualitative data reveal that prompt implementation of interactive technology to cope with social distancing during the pandemic added new routines to the staff workload. Using this interactive technology entailed new forms of collaborative work among residents, next of kin, health care professionals and technology facilitators. Additionally, the staff articulated a sense of responsibility towards using KOMP as a meaningful and practical tool for social communication in an extraordinary period of reduced social contact.

Conclusions
Improvised implementation of KOMP as an interactive technology shapes work routines, introduces new tasks and creates additional responsibilities. Despite creative efforts by health care staff, however, using KOMP remains constrained by the physical and cognitive abilities of its users. We suggest that health care managers ask a deceptively simple question when introducing novel technologies in health care contexts, namely: what kind of invisible work do these devices entail?
T-cell-lymphoma presented as a solitary subcutaneous mass in the ventral cervical region of an adult llama- diagnostic and treatment
Authors: Schoiswohl Julia , Eibl Cassandra , Haralambus Rhea , Lipnik Karoline , Schieder Katrin , Franz Sonja 
Published: February 2022

Abstract
Background
Neoplasm in South American camelids (SAC) are commonly described. The most frequently reported type of neoplasm are lymphomas and difference in the age suffering from lymphomas of and llamas is seen.
This report describes a case of a solitary lymphoma in a 5 years and 9 month old llama mare displaying the approach of diagnostic imaging and successful surgical treatment.

Case presentation
The llama was referred to the clinic for dyspnoea and inspiratory abnormal respiratory sounds. The clinical examination comprised blood cell count, ultrasonographic and radiographic examinations, endoscopy and fine needle aspiration cytology of a mass detected in the mid cervical region. The mass was surgically removed. Histopathological examination of the surgically removed mass diagnosed a malignant T-cell- lymphoma. According to the results of the clinical, ultrasonographic and radiographic examinations no tumor invasion was apparent in distant organs and the llama was discharged from the clinic seven days after surgery.

Conclusion
Lymphoma has been reported to be the most common neoplasia in camelids and are more often described in young alpacas and in adult llamas. To the author´s knowledge the case presented here is the first that described a broad panel of diagnostic tools including ultrasound, radiographs, endoscopy, fine needle aspiration cytology and histopathoogical examination as well as a successful surgical treatment of a solitary lymphoma in camelids.
Effect of previous wedge resection for interstitial pregnancy on pregnancy and neonatal outcomes following frozen-thawed embryo transfer (FET) cycles of IVF/ICSI: a retrospective study
Authors: Tang Shengluan , Du Tong , Huang Jialyu , Ye Hongjuan , Zhao Ming , Lin Jiaying , Kuang Yanping 
Published: February 2022

Abstract
Objective
The present study aimed to evaluate pregnancy and neonatal outcomes in women, with a previous history of wedge resection for interstitial pregnancy, in frozen-thawed embryo transfer (FET) cycles of IVF/ICSI.

Methods
The present study involved a retrospective case-control assessment of 75 cases and 375 control subjects over 6 years in a single center. To compare pregnancy and neonatal outcomes between cases, treated using wedge resection, and controls without any previous history of ectopic pregnancy, propensity score matching (1:5) was utilized. The study also compared subgroups in the case group.

Results
Women with previous wedge resection exhibited higher rates of ectopic pregnancy and uterine rupture rate as compared to control subjects (9.1% vs 1.3%, P = 0.025 and 4.5% vs 0%, P = 0.035, respectively). No statistically significant differences were recorded between the two cohorts with regard to clinical pregnancy rate, live birth rate, and neonatal outcomes. For pregnancy type subgroup analysis, Z-score and rates of large for gestational age were recorded to be significantly lower in twin pregnancy subgroup when compared with singleton pregnancy subgroup (0.10 (− 0.59, 0.25) vs 0.50 (− 0.97, 1.39), P = 0.005; 4.5% vs 26.1%, P = 0.047, respectively).

Conclusion
The results of the present study indicated that previous wedge resection correlated to a higher risk of ectopic pregnancy and uterine rupture. However, it might not be related to an increased risk of adverse neonatal outcomes. The study recommended cesarean section in these patients. Further studies are required to verify the validity of current recommendations.
Breast Cancers Are Immunogenic: Immunologic Analyses and a Phase II Pilot Clinical Trial Using Mutation-Reactive Autologous Lymphocytes
Authors: Zacharakis Nikolaos , Huq Lutfi M. , Seitter Samantha J. , Kim Sanghyun P. , Gartner Jared J. , Sindiri Sivasish , Hill Victoria K. , Li Yong F. , Paria Biman C. , Ray Satyajit , Gasmi Billel , Lee Chyi-chia , Prickett Todd D. , Parkhurst Maria R. , Robbins Paul F. , Langhan Michelle M. , Shelton Thomas E. , Parikh Anup Y. , Levi Shoshana T. , Hernandez Jonathan M. , Hoang Chuong D. , Sherry Richard M. , Yang James C. , Feldman Steven A. , Goff Stephanie L. , Rosenberg Steven A. 
Published: February 2022

PURPOSE Metastatic breast cancer (mBrCa) is most often an incurable disease with only modest responses to available immunotherapies. This study investigates the immunogenicity of somatic mutations in breast cancer and explores the therapeutic efficacy in a pilot trial of mutation-reactive tumor-infiltrating lymphocytes (TILs) in patients with metastatic disease. PATIENTS AND METHODS Forty-two patients with mBrCa refractory to previous lines of treatment underwent surgical resection of a metastatic lesion(s), isolation of TIL cultures, identification of exomic nonsynonymous tumor mutations, and immunologic screening for neoantigen reactivity. Clinically eligible patients with appropriate reactivity were enrolled into one cohort of an ongoing phase II pilot trial of adoptive cell transfer of selected neoantigen-reactive TIL, with a short course of pembrolizumab (ClinicalTrials.gov identifier: NCT01174121 ). RESULTS TILs were isolated and grown in culture from the resected lesions of all 42 patients with mBrCa, and a median number of 112 (range: 6-563) nonsynonymous mutations per patient were identified. Twenty-eight of 42 (67%) patients contained TIL that recognized at least one immunogenic somatic mutation (median: 3 neoantigens per patient, range: 1-11), and 13 patients demonstrated robust reactivity appropriate for adoptive transfer. Eight patients remained clinically eligible for treatment, and six patients were enrolled on a protocol of adoptive cell transfer of enriched neoantigen-specific TIL, in combination with pembrolizumab (≤ 4 doses). Objective tumor regression was noted in three patients, including one complete response (now ongoing over 5.5 years) and two partial responses (6 and 10 months). CONCLUSION Most patients with breast cancer generated a natural immune response targeting the expressed products of their cancer mutations. Adoptive transfer of TIL is a highly personalized experimental option for patients with mBrCa shown to be capable of mediating objective responses in this pilot trial and deserves further study.
Direct Compaction Drug Product Process Modeling
Authors: Russell Alexander , Strong John , Garner Sean , Ketterhagen William , Long Michelle , Capece Maxx 
Published: February 2022

AbstractMost challenges during the development of solid dosage forms are related to the impact of any variations in raw material properties, batch size, or equipment scales on the product quality and the control of the manufacturing process. With the ever pertinent restrictions on time and resource availability versus heightened expectations to develop, optimize, and troubleshoot manufacturing processes, targeted and robust science-based process modeling platforms are essential. This review focuses on the modeling of unit operations and practices involved in batch manufacturing of solid dosage forms by direct compaction. An effort is made to highlight the key advances in the past five years, and to propose potentially beneficial future study directions.
Policy Brief 4: Social norms, mental models and other behavioural drivers of petty corruption
Authors: Baez Camargo Claudia , Kassa Saba 
Published: February 2022

This policy brief summarises the main findings and lessons learned from research on corruption, social norms and behaviours in Tanzania. While the findings show that petty corruption is prevalent and results in inequitable public service delivery, they also inform that citizen and public officials’ attitudes and behaviours towards corruption are shifting as a result of changes in the political environment.
The evidence furthermore suggests that the effectiveness of conventional anti-corruption approaches may be enhanced by incorporating behavioural insights about entrenched social norms and collective understandings that are associated with practices of bribery and favouritism.