bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using the Kolb’s experiential learning cycle to explore the extent of application of one health competencies to solving global health challenges; a tracer study among AFROHUN-Uganda alumni
Authors: Ssekamatte Tonny , Isunju John Bosco , Nalugya Aisha , Mugambe Richard K. , Kalibala Patrick , Musewa Angella , Bikaako Winnie , Nattimba Milly , Tigaiza Arnold , Nakalembe Doreen , Osuret Jimmy , Wafula Solomon Tsebeni , Buregyeya Esther , Tsiouris Fatima , Michaels-Strasser Susan , Kabasa John David , Bazeyo William 
Published: May 2022

Abstract
Background
The Africa One Health University Network (AFROHUN) with support from the United States Agency for International Development (USAID), has since 2012 conducted pre and in-service One health (OH) trainings with the objective of improving global health security. These trainings aim to build competencies that, enhance a multidisciplinary approach to solving global health challenges. Despite the investment in OH trainings, there is limited documentation of the extent of acquisition and application of the OH competencies at workplaces. This tracer study explored the extent of acquisition and application of the OH competencies by the AFROHUN-Uganda alumni.

Methods
A cross-sectional study was conducted among a random sample of 182 AFROHUN-Uganda alumni of 2013–2018 cohorts. A blended approach of interviewer-administered and self-administered questionnaires was used. Virtual platforms such as Zoom, Microsoft teams, and Skype, and phone interviews were used to collect data when face-to-face interactions with alumni were not possible. Data were collected electronically, either through a link or with the aid of the KoboCollect mobile application, pre-installed on android enabled devices, and analysed using STATA14.0.

Results
The majority of respondents, 78.6% (143/182) had jobs that required application of OH knowledge and skills, 95.6% (174/182) had learned employable skills from OH activities and 89.6% (163/182) had applied such skills when searching for employment. About 21.7% (34/180) to a very high extent required OH field-specific theoretical knowledge at their workplaces, 27.4% (43/80) to a very high extent required OH field-specific practical knowledge/skills, 42.7% (67/180) to a high extent required a change in attitude and perceptions towards working with people from different disciplines, 49.0% (77/180) required collaboration and networking skills, and more than half, 51.0% (80/180) required team building skills.

Conclusions
The majority of OH alumni to a very high extent acquired and applied OH competences such as teamwork, effective communication, community entry and engagement, report writing and problem-solving skills. This study revealed the significant contribution of the AFROHUN Uganda OH activities towards supportive work environments, and highlights areas of improvement such as supporting the trainees to acquire people-management skills, innovation, and an entrepreneurial mind set.
Pressure pain thresholds in a real-world chiropractic setting: topography, changes after treatment, and clinical relevance?
Authors: Nim Casper G. , Aspinall Sasha L. , Weibel Rasmus , Steenfelt Martin G. , O’Neill Søren 
Published: May 2022

AbstractBackgroundChanges in pain sensitivity are a commonly suggested mechanism for the clinical effect of spinal manipulative therapy (SMT). Most research has examined pressure pain thresholds (PPT) and has primarily been conducted in controlled experimental setups and on asymptomatic populations. Many important factors are likely to differ between research and clinical settings, which may affect PPT changes following SMT. Therefore, we planned to investigate PPT before and after clinical chiropractic care and investigate relationships with various potentially clinically-relevant factors.MethodsWe recruited participants from four Danish chiropractic clinics between May and August 2021. A total of 129 participants (72% of the invited) were included. We measured PPT at eight pre-determined test sites (six spinal and two extra-spinal) immediately before (pre-session) and immediately after (post-session) the chiropractic consultation.We used regression analyses to investigate PPT changes, including the following factors: (i) vertebral distance to the nearest SMT site, (ii) rapid clinical response, (iii) baseline PPT, (iv) number of SMTs performed, (v) at the region of clinical pain compared to other regions, and (vi) if other non-SMT treatment was provided. We also performed topographic mapping of pre-session PPTs.ResultsAfter the consultation, there was a non-significant mean increase in PPT of 0.14 kg (95% CIs = − 0.01 to 0.29 kg). No significant associations were found with the distance between the PPT test site and nearest SMT site, the clinical response of participants to treatment, the pre-session PPT, the total number of SMTs performed, or the region/s of clinical pain. A small increase was observed if myofascial treatment was also provided. Topographic mapping found greater pre-session PPTs in a caudal direction, not affected by the region/s of clinical pain.ConclusionsThis study of real-world chiropractic patients failed to demonstrate a substantial local or generalized increase in PPT following a clinical encounter that included SMT. This runs counter to prior laboratory research and questions the generalizability of highly experimental setups investigating the effect of SMT on PPT to clinical practice.
Feasibility of postoperative spine stereotactic body radiation therapy in proximity of carbon and titanium hybrid implants using a robotic radiotherapy device
Authors: Henzen Dominik , Schmidhalter Daniel , Guyer Gian , Stenger-Weisser Anna , Ermiş Ekin , Poel Robert , Deml Moritz Caspar , Fix Michael Karl , Manser Peter , Aebersold Daniel Matthias , Hemmatazad Hossein 
Published: May 2022

AbstractBackground and purposeTo assess the feasibility of postoperative stereotactic body radiation therapy (SBRT) for patients with hybrid implants consisting of carbon fiber reinforced polyetheretherketone and titanium (CFP-T) using CyberKnife.Materials and methodsAll essential steps within a radiation therapy (RT) workflow were evaluated. First, the contouring process of target volumes and organs at risk (OAR) was done for patients with CFP-T implants. Second, after RT-planning, the accuracy of the calculated dose distributions was tested in a slab phantom and an anthropomorphic phantom using film dosimetry. As a third step, the accuracy of the mandatory image guided radiation therapy (IGRT) including automatic matching was assessed using the anthropomorphic phantom. For this goal, a standard quality assurance (QA) test was modified to carry out its IGRT part in presence of CFP-T implants.ResultsUsing CFP-T implants, target volumes could precisely delineated. There was no need for compromising the contours to overcome artifact obstacles. Differences between measured and calculated dose values were below 11% for the slab phantom, and at least 95% of the voxels were within 5% dose difference. The comparisons for the anthropomorphic phantom showed a gamma-passing rate (5%, 1 mm) of at least 97%. Additionally the test results with and without CFP-T implants were comparable. No issues concerning the IGRT were detected. The modified machine QA test resulted in a targeting error of 0.71 mm, which corresponds to the results of the unmodified standard tests.ConclusionDose calculation and delivery of postoperative spine SBRT is feasible in proximity of CFP-T implants using a CyberKnife system.
“Why them, why me, why us?” The experiences of parents of children with lysosomal acid lipase deficiency: an interpretative phenomenological analysis study
Authors: Hassall S. , Smith D. M. , Rust S. , Jones S. A. , Wittkowski A. 
Published: May 2022

AbstractBackgroundLysosomal acid lipase deficiency (LALD) is an ultra-rare, inherited metabolic disease within the category of lysosomal storage disorders, affecting an infant’s ability to metabolise cholesterol. Developments in treatment, including Enzyme Replacement Therapy, have proven successful, with some children living for a number of years with treatment, although the future still remains unknown. The aim of this study was to explore the lived experiences of parents of children with LALD.Main textParticipants were recruited from across the United Kingdom between 2020 and 2021. Eight parents (five mothers and three fathers) whose child had a confirmed diagnosis of LALD were interviewed. Data collected from the semi-structured interviews were audio-record, transcribed and analysed using Interpretative Phenomenological Analysis (IPA). Three superordinate and nine subordinate themes emerged from the data: (1)Uncertainty—a double-edged sword(plunged into an uncertain world, living life with worry and walking the tightrope of stability), (2)Powerless against a shared battle with LALD(a helpless parent, a joint battle, protection against distress and a vulnerable parent needing help) and 3)Accepting a life with LALD(coming to terms with a diagnosis of LALD and a hidden condition).ConclusionsThe findings of this study highlight that the diagnosis of LALD proves to be a very challenging and emotionally distressing time in parents’ lives, with increased uncertainty about what the future will hold for their child. This study signified the importance of healthcare pathways and service provisions to support parents and their children throughout diagnosis and beyond.
Clinical and genetic spectrums of 413 North African families with inherited retinal dystrophies and optic neuropathies
Authors: Bouzidi Aymane , Charoute Hicham , Charif Majida , Amalou Ghita , Kandil Mostafa , Barakat Abdelhamid , Lenaers Guy 
Published: May 2022

AbstractBackgroundInherited retinal dystrophies (IRD) and optic neuropathies (ION) are the two major causes world-wide of early visual impairment, frequently leading to legal blindness. These two groups of pathologies are highly heterogeneous and require combined clinical and molecular diagnoses to be securely identified. Exact epidemiological studies are lacking in North Africa, and genetic studies of IRD and ION individuals are often limited to case reports or to some families that migrated to the rest of the world. In order to improve the knowledge of their clinical and genetic spectrums in North Africa, we reviewed published data, to illustrate the most prevalent pathologies, genes and mutations encountered in this geographical region, extending from Morocco to Egypt, comprising 200 million inhabitants.Main bodyWe compiled data from 413 families with IRD or ION together with their available molecular diagnosis. The proportion of IRD represents 82.8% of index cases, while ION accounted for 17.8%. Non-syndromic IRD were more frequent than syndromic ones, with photoreceptor alterations being the main cause of non-syndromic IRD, represented by retinitis pigmentosa, Leber congenital amaurosis, and cone-rod dystrophies, while ciliopathies constitute the major part of syndromic-IRD, in which the Usher and Bardet Biedl syndromes occupy 41.2% and 31.1%, respectively. We identified 71 ION families, 84.5% with a syndromic presentation, while surprisingly, non-syndromic ION are scarcely reported, with only 11 families with autosomal recessive optic atrophies related toOPA7andOPA10variants, or with the mitochondrial related Leber ION. Overall, consanguinity is a major cause of these diseases within North African countries, as 76.1% of IRD and 78.8% of ION investigated families were consanguineous, explaining the high rate of autosomal recessive inheritance pattern compared to the dominant one. In addition, we identified many founder mutations in small endogamous communities.Short conclusionAs both IRD and ION diseases constitute a real public health burden, their under-diagnosis in North Africa due to the absence of physicians trained to the identification of inherited ophthalmologic presentations, together with the scarcity of tools for the molecular diagnosis represent major political, economic and health challenges for the future, to first establish accurate clinical diagnoses and then treat patients with the emergent therapies.
Tumor organoids: applications in cancer modeling and potentials in precision medicine
Authors: Xu Hanxiao , Jiao Dechao , Liu Aiguo , Wu Kongming 
Published: May 2022

AbstractCancer is a top-ranked life-threatening disease with intratumor heterogeneity. Tumor heterogeneity is associated with metastasis, relapse, and therapy resistance. These factors contribute to treatment failure and an unfavorable prognosis. Personalized tumor models faithfully capturing the tumor heterogeneity of individual patients are urgently needed for precision medicine. Advances in stem cell culture have given rise to powerful organoid technology for the generation of in vitro three-dimensional tissues that have been shown to more accurately recapitulate the structures, specific functions, molecular characteristics, genomic alterations, expression profiles, and tumor microenvironment of primary tumors. Tumoroids in vitro serve as an important component of the pipeline for the discovery of potential therapeutic targets and the identification of novel compounds. In this review, we will summarize recent advances in tumoroid cultures as an excellent tool for accurate cancer modeling. Additionally, vascularization and immune microenvironment modeling based on organoid technology will also be described. Furthermore, we will summarize the great potential of tumor organoids in predicting the therapeutic response, investigating resistance-related mechanisms, optimizing treatment strategies, and exploring potential therapies. In addition, the bottlenecks and challenges of current tumoroids will also be discussed in this review.
PIK3CA-related overgrowth with an uncommon phenotype: case report
Authors: Rotunno Roberta , Diociaiuti Andrea , Pisaneschi Elisa , Carnevale Claudia , Dentici Marialisa , El Hachem May 
Published: May 2022

Abstract
Background
Megalencephaly-capillary malformation syndrome is a rare multiple-malformation syndrome secondary to somatic activating mutations in the PI3K-AKT-MTOR pathway. This is included in a heterogeneous group of disorders, now defined “PIK3CA-related overgrowth spectrum”.

Case presentation
We report a 22-months-old female presenting an uncommon phenotype associated with a genetic mosaicism in the PIK3CA gene, detected on DNA extracted from blood peripheral and tissue biopsy.

Conclusions
NGS is the preferred method for molecular diagnosis of PROS on affected skin and overgrown tissues as primary samples. The wide phenotypic variability is based on the distribution of mosaicism, in fact the same mutation can cause different PIK3CA related disorders. Continuous understanding of the clinical spectrum and of molecular basis of PROS and their overlap will lead to improve diagnosis, management and new treatment strategies.
Clinical and biochemical endpoints and predictors of response to plasma exchange in septic shock: results from a randomized controlled trial
Authors: Stahl Klaus , Wand Philipp , Seeliger Benjamin , Wendel-Garcia Pedro David , Schmidt Julius J. , Schmidt Bernhard M. W. , Sauer Andrea , Lehmann Felix , Budde Ulrich , Busch Markus , Wiesner Olaf , Welte Tobias , Haller Hermann , Wedemeyer Heiner , Putensen Christian , Hoeper Marius M. , Bode Christian , David Sascha 
Published: May 2022

Abstract
Background
Recently, a randomized controlled trial (RCT) demonstrated rapid but individually variable hemodynamic improvement with therapeutic plasma exchange (TPE) in patients with septic shock. Prediction of clinical efficacy in specific sepsis treatments is fundamental for individualized sepsis therapy.

Methods
In the original RCT, patients with septic shock of < 24 h duration and norepinephrine (NE) requirement ≥ 0.4 μg/kg/min received standard of care (SOC) or SOC + one single TPE. Here, we report all clinical and biological endpoints of this study. Multivariate mixed-effects modeling of NE reduction was performed to investigate characteristics that could be associated with clinical response to TPE.

Results
A continuous effect of TPE on the reduction in NE doses over the initial 24 h was observed (SOC group: estimated NE dose reduction of 0.005 µg/kg/min per hour; TPE group: 0.018 µg/kg/min per hour, p = 0.004). Similarly, under TPE, serum lactate levels, continuously decreased over the initial 24 h in the TPE group, whereas lactate levels increased under SOC (p = 0.001). A reduction in biomarkers and disease mediators (such as PCT (p = 0.037), vWF:Ag (p < 0.001), Angpt-2 (p = 0.009), sTie-2 (p = 0.005)) along with a repletion of exhausted protective factors (such as AT-III (p = 0.026), Protein C (p = 0.012), ADAMTS-13 (p = 0.008)) could be observed in the TPE but not in the SOC group. In a multivariate mixed effects model, increasing baseline lactate levels led to greater NE dose reduction effects with TPE as opposed to SOC (p = 0.004).

Conclusions
Adjunctive TPE is associated with the removal of injurious mediators and repletion of consumed protective factors altogether leading to preserved hemodynamic stabilization in refractory septic shock. We identified that baseline lactate concentration as a potential response predictor might guide future designing of large RCTs that will further evaluate TPE with regard to hard endpoints.
Trial registration Retrospectively registered 18th January 2020 at clinicaltrials.gov (Identifier: NCT04231994).
Globally elevated excitation–inhibition ratio in children with autism spectrum disorder and below-average intelligence
Authors: Manyukhina Viktoriya O. , Prokofyev Andrey O. , Galuta Ilia A. , Goiaeva Dzerassa E. , Obukhova Tatiana S. , Schneiderman Justin F. , Altukhov Dmitrii I. , Stroganova Tatiana A. , Orekhova Elena V. 
Published: May 2022

AbstractBackgroundAltered neuronal excitation–inhibition (E–I) balance is strongly implicated in ASD. However, it is not known whether the direction and degree of changes in the E–I ratio in individuals with ASD correlates with intellectual disability often associated with this developmental disorder. The spectral slope of the aperiodic 1/f activity reflects the E–I balance at the scale of large neuronal populations and may uncover its putative alternations in individuals with ASD with and without intellectual disability.MethodsHerein, we used magnetoencephalography (MEG) to test whether the 1/f slope would differentiate ASD children with average and below–average (< 85) IQ. MEG was recorded at rest with eyes open/closed in 49 boys with ASD aged 6–15 years with IQ ranging from 54 to 128, and in 49 age-matched typically developing (TD) boys. The cortical source activity was estimated using the beamformer approach and individual brain models. We then extracted the 1/f slope by fitting a linear function to the log–log-scale power spectra in the high-frequency range.ResultsThe global 1/f slope averaged over all cortical sources demonstrated high rank-order stability between the two conditions. Consistent with previous research, it was steeper in the eyes-closed than in the eyes-open condition and flattened with age. Regardless of condition, children with ASD and below-average IQ had flatter slopes than either TD or ASD children with average or above-average IQ. These group differences could not be explained by differences in signal-to-noise ratio or periodic (alpha and beta) activity.LimitationsFurther research is needed to find out whether the observed changes in E–I ratios are characteristic of children with below-average IQ of other diagnostic groups.ConclusionsThe atypically flattened spectral slope of aperiodic activity in children with ASD and below-average IQ suggests a shift of the global E–I balance toward hyper-excitation. The spectral slope can provide an accessible noninvasive biomarker of the E–I ratio for making objective judgments about treatment effectiveness in people with ASD and comorbid intellectual disability.
Dried rhododendron flower ingestion presenting with bradycardia and hypotension: a case report
Authors: Baral Sushil , Baral Binaya Kumar , Sharma Pranit , Shrestha Surendra Lal 
Published: May 2022

Abstract
Background
Rhododendron toxicity can be a life-threatening situation when manifested; it results in bradycardia and hypotension. Treatment remains challenging when it is complicated with refractory hypotension involving the multiorgan system if not treated early.

Case presentation
A 33-year-old Magar male presented with history of ingestion of two handfuls of white rhododendron flower. He had ingested the flowers believing that it would help relieve the pain and remove the materials stuck in his food pipe. Symptoms presented included muscular discomfort, dizziness, nausea, palpitation, tingling sensation around the face and lips, difficulty breathing, chest tightness, and difficulty swallowing within 4–5 hours after the ingestion of the dried flower. High-flow oxygen, intravenous fluids, atropine, and other supportive measures were used during the emergency, followed later by transfer to the intensive care unit for further observation.

Conclusion
The patient was discharged with complete recovery after 2 days of hospital stay. Intentional or accidental ingestion of toxic plants can be severe or even life-threatening. Thus, clinicians should be familiar with local toxic plants with grayanotoxin action.
Epiregulin increases stemness-associated genes expression and promotes chemoresistance of non-small cell lung cancer via ERK signaling
Authors: Zhang Yujia , Qiu Fengjun , Ye Tingjie , Lee Sau Har , Xu Jiatuo , Jia Lingyan , Zeng Rui , Wang Xiaoling , Hu Xudong , Yan Xiaofeng , Li Hua , Lu Yanlin , Wang Xiaoling , Jiang Rilei , Xu Wei 
Published: May 2022

Abstract
Background
Chemoresistance often causes the failure of treatment and death of patients with advanced non-small-cell lung cancer. However, there is still no resistance genes signature and available enriched signaling derived from a comprehensive RNA-Seq data analysis of lung cancer patients that could act as a therapeutic target to re-sensitize the acquired resistant cancer cells to chemo-drugs. Hence, in this study, we aimed to identify the resistance signature for clinical lung cancer patients and explore the regulatory mechanism.

Method
Analysis of RNA-Seq data from clinical lung cancer patients was conducted in R studio to identify the resistance signature. The resistance signature was validated by survival time of lung cancer patients and qPCR in chemo-resistant cells. Cytokine application, small-interfering RNA and pharmacological inhibition approaches were applied to characterize the function and molecular mechanism of EREG and downstream signaling in chemoresistance regulation via stemness.

Results
The RTK and vitamin D signaling were enriched among resistance genes, where 6 genes were validated as resistance signature and associated with poor survival in patients. EREG/ERK signaling was activated by chemo-drugs in NSCLC cells. EREG protein promoted the NSCLC resistance to chemo-drugs by increasing stemness genes expression. Additionally, inhibition of EREG/ErbB had downregulated ERK signaling, resulting in decreased expression of stemness-associated genes and subsequently re-sensitized the resistant NSCLC cells and spheres to chemo-drugs.

Conclusions
These findings revealed 6 resistance genes signature and proved that EREG/ErbB regulated the stemness to maintain chemoresistance of NSCLC via ERK signaling. Therefore, targeting EREG/ErbB might significantly and effectively resolve the chemoresistance issue.