bluuebunny/crossref_metadata_2025 huggingface dataset:
Broad versus narrow organizational scope among nonprofits: The moderating effects of the task environment
Authors: Mmbaga Nick , Yan Jiaju Justin , Gras David
Published: July 2022

We use a mixed-methods design to investigate the relationship between scope and performance within nonprofits and under varying conditions of environmental dynamism, munificence, and complexity. Prior strategy research on for-profit organizations suggests that relatively high levels of environmental dynamism and complexity attenuate the negative relationship between scope and performance, while greater munificence reinforces it. Our longitudinal quantitative study of approximately 63,000 Canadian nonprofits suggests the opposite: greater dynamism reinforces the negative relationship, and munificence bears no definitive effect, indicating that certain task environment effects on the scope–performance relationship manifest uniquely for organizations pursuing social over economic value creation. We then conducted qualitative interviews with nonprofit executives to explore in greater detail the probable mechanisms that underpin these relationships, highlighting three— nature of mission, scarcity of human capital, and competitive tension in collaboration. We offer several contributions to theory and practice regarding the relationship between nonprofit scope and performance.
Stress Test
Authors: Burch Shanaé R.
Published: July 2022

Standard procedure prompts health professionals to ask, “Is Stress Causing My Patients’ Symptoms?” With acknowledgment of the visceral ways systemic oppression gets under the skin, the poem is a meditation on new possibilities for measuring and ameliorating stress. The author has been living with chronic hives since early 2016, and over the years, doctors have continued to suggest she focus on reducing sources of stress in her life. To view the original version of this poem, see the supplemental material section of this article online.
Approaches to spatially resolving the tumour immune microenvironment of hepatocellular carcinoma
Authors: Marsh-Wakefield Felix , Ferguson Angela L , Liu Ken , Santhakumar Cositha , McCaughan Geoffrey , Palendira Umaimainthan
Published: July 2022

Hepatocellular carcinoma (HCC) is a common and deadly cancer worldwide. Many factors contribute to mortality and place an individual at high risk of developing HCC, including viral infection, alcohol intake, metabolic-associated disease, autoimmunity and genetic liver disorders. Although there are many therapeutics available, much about this disease remains to be understood. This is most evident when investigating the tumour microenvironment (TME). Both innate and adaptive immune cells have been associated with carcinogenesis within the TME of HCC patients. The ability to interrogate the TME more thoroughly with spatial technologies continues to improve, both at the experimental and analytical stages. This review provides insight into technologies available to investigate the TME, and how such technologies are beneficial for improving our understanding of HCC carcinogenesis.
Changes in ultrasound imaging of joints, entheses, bursae and tendons 24 and 48 h after adjusted weight training
Authors: Schreiner Julia K. , Recker Florian , Scheicht Dennis , Karakostas Pantelis , Ziob Jana , Behning Charlotte , Preuss Peter , Brossart Peter , Schäfer Valentin S.
Published: July 2022

Background:

Joint effusion and enthesitis are common ultrasound findings in rheumatic diseases such as rheumatoid arthritis or spondyloarthritis. However, changes of joints and entheses were not only observed in patients but also in physically active individuals and athletes.

Objectives:

The purpose of this study was to evaluate joint, entheseal, bursal and tendon musculoskeletal ultrasound (MSUS) findings in large and medium joints of young healthy individuals after completing a standardised weight training.

Design:

This is a prospective cohort study.

Methods:

MSUS examinations of large- and medium-sized joints, and related entheseal sites, bursae and tendons were performed on young healthy individuals (ages 18–30 years). Before, 24 and 48 h after completing 1 h of standardised weight exercise, the subjects were evaluated by MSUS. The development of the MSUS findings and associated effects were examined using generalised linear mixed effects models.

Results:

In total, 51 healthy individuals (52.9% female) with a mean age of 23.7 (±2.5) years were enrolled. The results showed an increase in the number of individuals with at least one joint effusion from 37 (72.5%) before the weight training to 48 (94.1%) after 48 h. Entheses with pathologies were observed in 14 participants (27.5%) at baseline, increasing to 29 participants (56.9%) 48 h after the weight training. Biceps tendon sheath effusion was detected in 9 individuals (17.6%) prior to training, rising to 22 individuals (43.1%) after 48 h. A significant increase in the number of joints with effusion and abnormal entheses within 48 h after the weight training was indicated by the generalised linear mixed effects models.

Conclusion:

Within 48 h after the weight training session, a significant increase in the prevalence of joint effusion in large and medium joints and the prevalence of abnormal entheses was observed. As a result, when performing and interpreting an MSUS examination, the patient’s physical activities should be taken into account.
Time to Achieving Clinically Significant Outcomes After Meniscal Allograft Transplantation
Authors: Huddleston Hailey P. , Polce Evan M. , Gilat Ron , Mehta Nabil , Alzein Mohamad , Dandu Navya , Parvaresh Kevin C. , Cole Brian J. , Yanke Adam B.
Published: July 2022

Purpose

To determine the time to achieving minimal clinically important difference (MCID) and patient acceptable symptomatic state (PASS) for commonly administered patient-reported outcome (PRO) measures and risk factors affecting achievement of clinically significant outcomes in patients undergoing meniscal allograft transplantation (MAT).

Methods

A prospectively maintained MAT registry was retrospectively reviewed from April 2014 to May 2019. Patients who underwent revision MAT or did not complete preoperative PROs or one post operative time point were excluded. Patients who underwent concomitant procedures were included in the analysis. PROs were administered preoperatively and at 6 months, 1 year, and 2 years postoperatively. Previously defined MCID and PASS thresholds were utilized and Kaplan-Meier survival curve analysis with interval censoring was used to calculate the cumulative percentages of MCID and PASS achievement at each follow-up time interval (5-7, 11-13, and 23-25 months).

Results

Eighty patients (age: 28.35 ± 9.76, 50% male) who completed preoperative, 6-month ( n = 69, 86% compliance), and 1-year ( n = 76, 95% compliance) PROs were included. The majority of patients (>50%) achieved MCID and PASS on most included PROs. Workers’ compensation status was found to significantly delay achievement of MCID and PASS on all PROs except for PASS on Knee Injury and Osteoarthritis Outcome Score (KOOS) quality of life (QoL). Higher body mass index (BMI) significantly delayed time to achieving MCID on KOOS Pain and activities of daily living (ADL), as well as PASS on KOOS Symptoms and KOOS QoL.

Conclusion

This study suggests that the majority of patients have clinically significant improvements in pain and function after MAT, with more than 50% of patients experiencing clinically significant improvement within the first postoperative year. Workers’ compensation status and high BMI may prolong time to achievement of MCID and PASS after MAT.
Timing of osteoporosis therapies following fracture: the current status
Authors: Palui Rajan , Durgia Harsh , Sahoo Jayaprakash , Naik Dukhabandhu , Kamalanathan Sadishkumar
Published: July 2022

In most patients, osteoporosis is diagnosed only after the occurrence of the first fragility fracture. It is of utmost importance to start osteoporosis medications immediately in these patients to prevent future fractures and also to reduce associated mortality and morbidity. There remains a hesitancy over initiating osteoporotic medications, specifically for antiresorptive agents like bisphosphonates following an acute fracture due to concern over their effect on fracture healing. The purpose of this review is to study the effect of the timing of initiation of different osteoporosis medications on healing after an acute fracture. Most of the human studies, including randomized control trials (RCTs), did not find any significant negative effect on fracture healing with early use of bisphosphonate after an acute fracture. Anabolic agents like teriparatide have shown either neutral or beneficial effects on fracture healing and thus can be started very early following any osteoporotic fracture. Although human studies on the early use of other osteoporosis medications like denosumab or strontium ranelate are very sparse in the literature, none of these medications have shown any evidence of delay in fracture healing. To summarize, among the commonly used anti-osteoporosis agents, both bisphosphonates and teriparatide are safe to be initiated in the early acute post-fracture period. Moreover, teriparatide has shown some evidence in favor of reducing fracture healing time.
Long-term mortality rates of young stroke in Taiwan: A decade-long epidemiology population-based study
Authors: Wu Yu-ying , Chen Po-Yuan , Wu Cheng-Chun , Chen Han-Jung , Liang Cheng-Loong , Lee Yi-Che , Lin Chi-Wei , Hung Chao-Ming , Lin I-Fan , Wang Hao-Kuang
Published: July 2022

Introduction:

Stroke remains a leading cause of death worldwide. Stroke in young adults is an important issue, gaining extra attention in recent years. This study aims to investigate the mortality after stroke in young adults in Taiwan.

Patients and methods:

This is a registry- and population-based study in Taiwan of patients aged 20–50 years with first-ever stroke between 1999 and 2012, with follow-up until January 1, 2022. Patients and mortalities were identified through Taiwan National Health Insurance database.

Results:

The study population included 65,097 patients with stroke (mean age, 42.6 ± 6.6 years; 30.5% woman). There were 23,481 (36.1%) intracranial hemorrhage, 37,522 (57.6%) ischemic stroke, and 4094 (6.3%) stroke not otherwise specified. At the end of follow-up, a total of 18,248 deaths (28.0%) occurred during a median follow-up of 9.8 years (interquartile range, 6.4–13.7 years).

Conclusion:

Taiwan young adults who were 30-day survivors of first-ever stroke have significantly higher long-term mortality rates when compared to other population-based studies.
Spatiotemporal assessment of immunogenomic heterogeneity in multiple myeloma
Authors: Merz Maximilian , Hu Qiang , Merz Almuth Maria Anni , Wang Jie , Hutson Nicholas , Rondeau Cherie , Celotto Kimberly , Belal Ahmed , Alberico Ronald , Block AnneMarie W. , Mohammadpour Hemn , Wallace Paul K. , Tario Joseph , Luce Jesse , Glenn Sean T. , Singh Prashant , Samur Mehmet , Munshi Nikhil , Liu Song , McCarthy Philip L. , Wei Lei , Hillengass Jens
Published: July 2022

Spatial heterogeneity is a common phenomenon in metastatic solid tumors and an evolving concept in multiple myeloma (MM). The interplay between malignant plasma cells (PCs) and the microenvironment has not yet been analyzed in MM. For this purpose, we performed bone marrow aspirates and imaging-guided biopsies of corresponding lesions in newly diagnosed MM (NDMM) and relapsed/refractory MM (RRMM) patients. PCs were isolated and subjected to whole-exome sequencing (WES). Non-PCs were studied with next-generation flow (NGF) and T-cell receptor sequencing (TCRseq) to analyze the connection between malignant and nonmalignant cells in the bone marrow and in lesions. Although we observed a strong overlap from WES, NGF, and TCRseq in patients with intramedullary disease, WES revealed significant spatial heterogeneity in patients with extramedullary disease. NGF showed significant immunosuppression in RRMM compared with NDMM as indicated by fewer myeloid dendritic cells, unswitched memory B cells, Th9 cells, and CD8 effector memory T cells but more natural killer and regulatory T cells. Additionally, fewer T-cell receptor (TCR) sequences were detected in RRMM compared with NDMM and healthy individuals. After induction therapy, TCR repertoire richness increased to levels of healthy individuals, and NGF showed more regulatory T cells and myeloid-derived suppressor cells, regardless of depth of response. Clinical significance of imaging-guided biopsies of lesions was demonstrated by detection of monoclonal PCs in patients without measurable residual disease (MRD) in aspirates from the iliac crest as well as identification of secondary primary malignancies in MRD− patients. Furthermore, site-specific clones with different drug susceptibilities and genetically defined high-risk features were detected by our workflow.
Development and performance of a hereditary hemorrhagic telangiectasia-specific quality-of-life instrument
Authors: Kasthuri Raj S. , Chaturvedi Shruti , Thomas Sonia , Vandergrift Nathan , Bann Carla , Schaefer Nicole , Clancy Marianne S. , Pyeritz Reed , McCrae Keith R.
Published: July 2022

Hereditary hemorrhagic telangiectasia (HHT) is characterized by arteriovenous malformations and telangiectasia, with primary clinical manifestations of epistaxis and gastrointestinal bleeding and resultant anemia. HHT negatively affects health-related quality of life (HR-QoL); however, existing tools to measure HR-QoL are not HHT specific. Our objective was to develop an HHT-specific HR-QoL (HHT-QoL) instrument and evaluate its performance in a cross-sectional survey of individuals with HHT. Four HHT-specific questions were developed to evaluate the impact of HHT on productivity and social and personal interactions. An anonymous e-mail survey was conducted through Cure HHT. Participants also indicated their perceived HHT severity and completed 3 Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaires: Discretionary Social Activities, Social Roles, and Emotional Distress. Complete data were available for 290 participants who self-identified their HHT severity as mild (29%), moderate (46%), or severe (25%). The HHT-QoL scale was reliable (Cronbach’s-α, 0.83). Principal components analysis indicated the instrument was unidimensional. Participants had low levels of QoL with their ability to participate in discretionary social activities (PROMIS mean 36.4 [standard deviation 14.3]) and perform in social roles (41.5 [17.2]), and the presence of a high level of emotional distress (64.8 [24.2]). The HHT-QoL score correlated negatively with PROMIS Discretionary Social Activities (r = −0.65) and Social Roles (r = −0.68) and positively correlated with PROMIS Emotional Distress (r = 0.51). In conclusion, the 4-item HHT-QoL instrument provides valuable insight and may be a useful addition to future clinical research in HHT.
Accuracy benchmark of the GeneMind GenoLab M sequencing platform for WGS and WES analysis
Authors: Li Chaoyang , Fan Xue , Guo Xin , Liu Yongfeng , Wang Miao , Zhao Xiao Chao , Wu Ping , Yan Qin , Sun Lei
Published: July 2022

Background

GenoLab M is a recently developed next-generation sequencing (NGS) platform from GeneMind Biosciences. To establish the performance of GenoLab M, we present the first report to benchmark and compare the WGS and WES sequencing data of the GenoLab M sequencer to NovaSeq 6000 and NextSeq 550 platform in various types of analysis. For WGS, thirty-fold sequencing from Illumina NovaSeq platform and processed by GATK pipeline is currently considered as the golden standard. Thus this dataset is generated as a benchmark reference in this study.

Results

GenoLab M showed an average of 94.62% of Q20 percentage for base quality, while the NovaSeq was slightly higher at 96.97%. However, GenoLab M outperformed NovaSeq or NextSeq at a duplication rate, suggesting more usable data after deduplication. For WGS short variant calling, GenoLab M showed significant accuracy improvement over the same depth dataset from NovaSeq, and reached similar accuracy to NovaSeq 33X dataset with 22x depth. For 100X WES, the F-score and Precision in GenoLab M were higher than NovaSeq or NextSeq, especially for InDel calling.

Conclusions

GenoLab M is a promising NGS platform for high-performance WGS and WES applications. For WGS, 22X depth in the GenoLab M sequencing platform offers a cost-effective alternative to the current mainstream 33X depth on Illumina.
Production and optimization of bioplastic (Polyhydroxybutyrate) from Bacillus cereus strain SH-02 using response surface methodology
Authors: Hamdy Shereen M. , Danial Amal W. , Gad El-Rab Sanaa M. F. , Shoreit Ahmed A. M. , Hesham Abd El-Latif
Published: July 2022

Background

Polyhydroxybutyrate (PHB) is a biopolymer formed by some microbes in response to excess carbon sources or essential nutrient depletion. PHBs are entirely biodegradable into CO2 and H2O under aerobic and anaerobic conditions. It has several applications in various fields such as medicine, pharmacy, agriculture, and food packaging due to its biocompatibility and nontoxicity nature.

Result

In the present study, PHB-producing bacterium was isolated from the Dirout channel at Assiut Governorate. This isolate was characterized phenotypically and genetically as Bacillus cereus SH-02 (OM992297). According to one-way ANOVA test, the maximum PHB content was observed after 72 h of incubation at 35 °C using glucose and peptone as carbon and nitrogen source. Response surface methodology (RSM) was used to study the interactive effects of glucose concentration, peptone concentration, and pH on PHB production. This result proved that all variables have a significant effect on PHB production either independently or in the interaction with each other. The optimized medium conditions with the constraint to maximize PHB content and concentration were 22.315 g/L glucose, and 15.625 g/L peptone at pH 7.048. The maximum PHB content and concentration were 3100.799 mg/L and 28.799% which was close to the actual value (3051 mg/l and 28.7%). The polymer was identified as PHB using FTIR, NMR, and mass spectrometry. FT-IR analysis showed a strong band at 1724 cm− 1 which attributed to the ester group’s carbonyl while NMR analysis has different peaks at 169.15, 67.6, 40.77, and 19.75 ppm that were corresponding to carbonyl, methine, methylene, and methyl resonance. Mass spectroscopy exhibited molecular weight for methyl 3- hydroxybutyric acid.

Conclusion

PHB–producing strain was identified as Bacillus cereus SH-02 (OM992297). Under optimum conditions from RSM analysis, the maximum PHB content and concentration of this strain can reach (3100.799 mg/L and 28.799%); respectively. FTIR, NMR, and Mass spectrometry were used to confirm the polymer as PHB. Our results demonstrated that optimization using RSM is one of the strategies used for reducing the production cost. RSM can determine the optimal factors to produce the polymer in a better way and in a larger quantity without consuming time.
Diagnosis and treatment of splenic torsion in children: preoperative thrombocytosis predicts splenic infarction
Authors: Wang Zengmeng , Peng Chunhui , Wu Dongyang , Wang Kai , Chen Yajun
Published: July 2022

Background

Pediatric splenic torsion is a rare entity, and the most common cause is wandering spleen. This study aimed to summarize our clinical experience in the diagnosis and surgical treatment pediatric patients with splenic torsion, and to use preoperative thrombocytosis as a preoperative predictive factor for splenic infarction.

Methods

From January 1st, 2016 to December 31st, 2021, 6 children diagnosed as splenic torsion were included. All patients were surgically treated and followed up. The clinical data was collected including clinical presentations, laboratory tests, imaging results, surgical procedures, and prognosis. Clinical experience of diagnosis and surgical treatment were summarized.

Results

There were 4 females and 2 males, with median age at surgery 102.6 (range 9.4–170.7) months. Abdominal pain and abdominal mass were the most common presentations. The diagnosis of splenic torsion depended on imaging studies, and adjacent organ involvement (gastric and pancreas torsion) was observed on contrast CT in one patient. Five patients were diagnosed as torsion of wandering spleen, and one was torsion of wandering accessory spleen. Emergent laparoscopic or open splenectomy was performed in all patients. Pathology revealed total splenic infarction in 4 patients, partial infarction in 1 patient, and viable spleen with congestion and hemorrhage in 1 patient. Preoperative platelet counts were elevated in all 4 patients with splenic infarction, but normal in the rest 2 with viable spleen. Postoperative transient portal vein branch thromboembolism occurred in one patient.

Conclusions

Imaging modalities are crucial for the diagnosis of pediatric splenic torsion and adjacent organ involvement. Preoperative thrombocytosis may predict splenic infarction. Spleen preserving surgery should be seriously considered over splenectomy in patients with a viable spleen.
Metformin activates Wnt/β-catenin for the treatment of diabetic osteoporosis
Authors: Huang Xiaopeng , Li Siyun , Lu Wenjie , Xiong Longjiang
Published: July 2022

Background

With the deepening of social aging, the incidence rate of osteoporosis and diabetes continues to rise. More and more clinical studies show that diabetes is highly correlated with osteoporosis. Diabetes osteoporosis is considered as a metabolic bone disease of diabetes patients. This study aims to explore the role and mechanism of metformin (Met) in diabetic osteoporosis.

Methods

Mouse MC3T3-E1 cells were treated with Met (0.5 mM) and exposed to high glucose (HG, 35 mM). The cells were cultured in an osteogenic medium for osteogenic differentiation, and the cell proliferation ability was determined using Cell Counting Kit-8; Alkaline phosphatase (ALP) activity detection and alizarin red staining were utilized to evaluate the effect of Met on MC3T3-E1 osteogenic differentiation. Western blot was used to detect the expressions of osteogenesis-related proteins (Runx2 and OCN) as well as Wnt/β-catenin signaling pathway-related proteins in MC3T3-E1 cells.

Results

HG inhibited proliferation and calcification of MC3T3-E1 cells, down-regulated ALP activity, and the expression of Runx2 and OCN in MC3T3-E1 cells. Meanwhile, the activity of the Wnt/β-catenin signaling pathway was inhibited. Met treatment was found to significantly stimulate the proliferation and calcification of MC3T3-E1 cells under HG conditions, as well as increase the ALP activity and the protein expression level of Runx2 and OCN in the cells. As a result, osteogenic differentiation was promoted and osteoporosis was alleviated. Apart from this, Met also increased the protein expression level of Wnt1, β-catenin, and C-myc to activate the Wnt/β-catenin signaling pathway.

Conclusion

Met can stimulate the proliferation and osteogenic differentiation of MC3T3-E1 cells under HG conditions. Met may also treat diabetic osteoporosis through Wnt/β-catenin activation.
Management of the COVID-19 pandemic: challenges, practices, and organizational support
Authors: Hossny Eman Kamel , Morsy Sahar Mohamed , Ahmed Asmaa Mohamed , Saleh Manal Saleh Moustafa , Alenezi Atallah , Sorour Marwa Samir
Published: July 2022

Background

Health organizations currently face tremendous challenges in the management of the COVID-19 pandemic. To do this, successful and proven scientific practices and support are needed.

Aim

This study aimed to explore the challenges, practices, and organizational support dealt with by nursing managers in the management of the COVID-19 pandemic.

Method

A qualitative content analysis study evaluated 35 nursing managers in five university hospitals through a semi-structured interview. The Consolidated Criteria for Reporting Qualitative Research were used for this qualitative study.

Results

Three main themes emerged: Challenges include the development of a COVID-19 crisis management plan, a shortage in nursing staff, and psychological problems. Practices include; changes in work schedules for nursing staff, the exchange process, hospital preparation, and training and education. And organizational support includes both support at an organizational level and support at an individual level.

Conclusion

This study revealed that nursing managers are faced with many challenges in the management of COVID-19, requiring good practices and organizational support. This study offers evidence for nursing managers to expect problems that may arise during the pandemic.

Recommendations

The COVID-19 pandemic requires the development of an integrated plan, and this plan must be disseminated to the hospital’s nursing and medical teams to better equip them for the current and future crises.
Nursing students’ use of social media in their learning: a case study of a Canadian School of Nursing
Authors: Giroux Catherine M. , Moreau Katherine A.
Published: July 2022

Background

Social media has diverse applications for nursing education. Current literature focuses on how nursing faculty use social media in their courses and teaching; less is known about how and why nursing students use social media in support of their learning.

Objectives

The purpose of this study was to explore how nursing students use social media in their learning formally and informally.

Methods

This exploratory qualitative case study of a Canadian School of Nursing reports on the findings of interviews (n = 9) with nursing students to explore how they use social media in their learning. Data were analyzed using a combined deductive and inductive coding approach, using three cycles of coding to facilitate category identification.

Results and conclusions

The findings demonstrate that participants use social media for formal and informal learning and specifically, as a third space to support their learning outside of formal institutional structures. Social media plays a role in the learning activities of nursing students studying both face-to-face and by distance. Accordingly, social media use has implications for learning theory and course design, particularly regarding creating space for student learning communities.
Development and validation of a self-care scale for older adults undergoing hip fracture surgery: the HFS-SC
Authors: Jeon Eun-Jeong , Sohng Kyeong-Yae , Yeom Hye-Ah
Published: July 2022

Background

The ability to take care of oneself after hip fracture surgery is important for older adults. Various scales have been developed for evaluation of this ability, but a scale specifically focusing on hip fracture has not been developed. The aim of this study was to develop and validate a scale (Hip Fracture Surgery Self-Care Scale, HFS-SC) to evaluate self-care for older adults undergoing hip fracture surgery.

Methods

The scale was developed according to the guidelines by DeVellis. Initial items were derived from a literature review and individual interviews with 11 older adults who underwent hip fracture surgery. To confirm the suitability of the questions, a preliminary survey was conducted on 25 older adults. Psychometric testing was performed on 300 older adults 65 years old or over living at home after surgery for hip fracture. Psychometric properties of the scale were examined by content validity, construct validity, concurrent validity, internal consistency reliability, and test-retest reliability.

Results

Exploratory factor analysis and confirmatory factor analysis demonstrated that the 18-item scale comprised five factors (functional independence, symptom recognition and management, positive mental health, participation and support in social activities, and a safe environment). The results of EFA showed that the factor loadings ranging from 0.51 to 0.87. The results of CFA were χ2=375.83, χ2/df=2.14, RMSEA 0.07, SRMR 0.05, GFI 0.88, TLI 0.91, and CFI 0.92 for the 18-item scale. The reliabilities of the scale were 0.91 for Cronbach’s alpha and 0.82 for test-retest reliability.

Conclusions

The HFS-SC has acceptable validity and reliability and is expected to be useful for evaluating the levels of self-care for older adults undergoing hip fracture surgery and adjusting at the post-fracture period at the community or out-patient department.
National and transnational drug shortages: a quantitative descriptive study of public registers in Europe and the USA
Authors: Ravela Reko , Lyles Alan , Airaksinen Marja
Published: July 2022

Background

Drug shortages are a growing global problem, posing clinical and economic challenges. To understand them better, we conducted an inventory of national public drug shortage registers and their comparability in Europe and the USA.

Methods

The study was based on openly accessible drug shortage notifications published by national drug authorities. These data were obtained from all national data sources mentioned on the European Medicines Agency’s (EMA’s) web page and FDA in the USA. After selection of the countries with comparable data, descriptive statistics were used to present characteristics of the shortages both across countries and within countries for 9 months (January–September) in 2020. We studied whether the shortages that occurred in these countries were the same, and how shortages were distributed by therapeutic uses and formulations. We also investigated price variation between the United States and Finland among drugs in shortage in one formulation category (creams and gels).

Results

Finland, Sweden, Norway, Spain, and the United States had suitable registers and were included. Altogether 5132 shortage reports from Finland (n = 1522), Sweden (n = 890), Norway (n = 800), Spain (n = 814), and the United States (n = 1106) were published during the study period. Of active ingredient level shortages 54% occurred in only one country, and 1% occurred in all five. However, at the country level, where there was one or more shortage notifications in an ATC active ingredient category, 19–41% were in a single country.

The distributions by ATC therapeutic class and drug formulation differed substantially between countries, particularly between the USA and European countries. Injectables had a high shortage risk in the USA (57% of all shortages versus 17–31% of all shortages in the European countries). By contrast, shortages in gels and creams occurred only in European data (4–6% of all shortages). In the price comparison, creams and gels in shortage in Finland were 160% more expensive in the USA where these shortages were not detected.

Conclusions

Public drug shortage registers are vital data sources for proactively maintaining and managing a reliable drug supply. However, our study demonstrates that much work remains to standardize the contents and quality of public register data.

Shortages may not be solely a consequence of manufacturing disruptions but may reflect other contributing factors in the international drug distribution and supply mechanisms, including price differences and profit margins between national pharmaceutical markets. Data to perform practical and useful international comparisons to understand these shortages are required.
Evaluation of the prevalence of congenital sensorineural deafness in a population of 72 client-owned purebred white cats examined from 2007 to 2021
Authors: Annemarie Kortas , Liliana Rytel , Małgorzata Kołecka , Andrzej Pomianowski
Published: July 2022

Background

Data on sensorineural deafness (CSD) in purebred white client-owned cats is limited as most of the information on this disease entity is assured from mixed-breed experimental colonies. It is known that cats with blue irises are more predisposed to CSD having been described as a condition in which many structures in the inner ear are damaged resulting in hearing loss. Cats with CSD are born deaf or lose their hearing irreversibly within the first 4-5 weeks of life. It is important to diagnose cats with this hereditary condition in order to eliminate affected individuals from breeding. The objectives of this study were to ensure data on prevalence of CSD in a population of 72 client-owned purebred white cats in Poland according to the color of the irises and to determine if there are any predispositions with regard to CSD among different breeds of cats in which the dominant W gene is present.

Results

Conducted study included 72 purebred white cats from six different breeds. The prevalence of CSD in the conducted study was 16.7%, CI95 [8.9%; 23.3%]. Unilateral deafness (11.1%, CI95 [4.9%; 20.7%]) was more common than bilateral CSD (5.6%, CI95 [1.5%; 13.6%]). The studies did not show any association between sex and CSD, p = .46. No association between the blue color of irises and deafness in the studied population could be found, p = .91. When compared to the rest of the examined population, no association was found between CSD and a particular breed.

Conclusions

Overall prevalence of CSD regarding the examined population of purebred client-owned cats was reported as lower when compared to previous studies concerning purebred cats. Cats with blue irises are more likely to be deaf in accordance to the current state of knowledge, however in the conducted study, no significant association between the presence of blue irises and deafness in white purebred cats could be identified. In order to eliminate CSD from the population, it is necessary to conduct examinations and diagnose CSD in white cats with blue irises as well as with irises of color other than blue. Association between particular breed and CSD wasn’t identified.
Low transmission rates of Equine infectious anemia virus (EIAV) in foals born to seropositive feral mares inhabiting the Amazon delta region despite climatic conditions supporting high insect vector populations
Authors: Resende Cláudia Fideles , Santos Alison Miranda , Cook Richard Frank , Victor Raphael Mattoso , Câmara Rebeca Jéssica Falcão , Gonçalves Gilberto Pereira , Lima Juliana Gonçalves , Maciel e Silva André Guimarães , Leite Romulo Cerqueira , dos Reis Jenner Karlisson Pimenta
Published: July 2022

Background

Marajó Island, within in the Amazon River Delta, supports numerous bands of feral equids including the genetically distinct Marajoara horses. Approximately 40% of the equids on the island are infected with Equine infectious anemia virus (EIAV). This high seropositivity rate coupled with the need to preserve rare breeds such as the Marajoara horse precludes euthanasia as the primary means for controlling EIAV in this region. In the absence of iatrogenic transmission, spread of this lentivirus is mediated primarily by hematophagous insects, whose year-round prevalence on the island is supported by favorable climatic conditions. In addition, cases of vertical EIAV transmission have been observed suggesting inclusion of seropositive mares in restorative breeding programs could result in their progeny becoming infected with this virus either pre-parturition or post-partum via hematophagous insects. Therefore, the aim of this study was to evaluate EIAV vertical and post-partum insect-mediated transmission rates among foals born to seropositive feral mares until natural weaning. Serum samples from foals born to seropositive feral mares within the Soure municipality, of Marajó Island, were collected to investigate their serological status, using an indirect ELISApgp45, with positive samples confirmed using the classical agar gel immunodiffusion (AGID) assay.

Results

The serological status of 28 foals were monitored over a 2-year period with some subjects, depending on their date of birth, being sampled up to six times. All foals remained with their respective mares until fully weaned at approximately 10 months of age. Only 2 foals (7.14%) in the study group became seropositive against EIAV.

Conclusion

The results demonstrate that in most cases it is possible to obtain seronegative foals born to and eventually weaned by EIA positive mares, even in equatorial regions where substantial rainfall and high temperatures favor the proliferation of insect vectors.
Association between the atherogenic index of plasma and major adverse cardiovascular events among non-diabetic hypertensive older adults
Authors: Hang Fei , Chen Jieruo , Wang Zefeng , Zheng Keyang , Wu Yongquan
Published: July 2022

Background

Literature on the association between the atherogenic index of plasma (AIP) and the risk of major adverse cardiovascular events (MACEs) among non-diabetic hypertensive older adults is quite limited.

Methods

A post-hoc analysis of data obtained from the Systolic Blood Pressure Intervention Trial was performed. The predictive value of AIP on the risk of MACEs among non-diabetic hypertensive older adults was assessed to evaluate whether the benefit of intensive blood pressure (BP) control in preventing MACEs is consistent in different AIP subgroups.

Results

In this study, 9323 participants with AIP were included, out of which 561 (6.02%) had composite cardiovascular outcomes during a median of 3.22 years of follow-up. Patients in the highest AIP quartile had a significantly increased risk of the primary outcome. In the fully adjusted Model 3, the adjusted hazard ratios (HRs) of the primary outcome for participants in Q2, Q3, and Q4 of AIP were 1.32 (1.02, 1.72), 1.38 (1.05, 1.81), and 1.56 (1.17, 2.08) respectively. Consistently, the trend test for the association between AIP quartiles and the primary outcome showed that a higher AIP quartile was associated with a significantly higher risk of the primary outcome (adjusted HR (95%CI) in model 3:1.14 (1.04, 1.25), P = 0,004). However, within each AIP quartile, absolute event rates were lower in the intensive treatment group. No evidence was found for the interaction between intensive BP control and AIP for the risk of the primary outcome (P for interaction = 0.932).

Conclusion

This study found that elevated AIP was independently and positively associated with the risk of MACEs among non-diabetic hypertensive older adults. The benefits of intensive BP control in managing cardiovascular events were consistent in different AIP subgroups.
Egocentric vision-based detection of surfaces: towards context-aware free-living digital biomarkers for gait and fall risk assessment
Authors: Nouredanesh Mina , Godfrey Alan , Powell Dylan , Tung James
Published: July 2022

Background

Falls in older adults are a critical public health problem. As a means to assess fall risks, free-living digital biomarkers (FLDBs), including spatiotemporal gait measures, drawn from wearable inertial measurement unit (IMU) data have been investigated to identify those at high risk. Although gait-related FLDBs can be impacted by intrinsic (e.g., gait impairment) and/or environmental (e.g., walking surfaces) factors, their respective impacts have not been differentiated by the majority of free-living fall risk assessment methods. This may lead to the ambiguous interpretation of the subsequent FLDBs, and therefore, less precise intervention strategies to prevent falls.

Methods

With the aim of improving the interpretability of gait-related FLDBs and investigating the impact of environment on older adults’ gait, a vision-based framework was proposed to automatically detect the most common level walking surfaces. Using a belt-mounted camera and IMUs worn by fallers and non-fallers (mean age 73.6 yrs), a unique dataset (i.e., Multimodal Ambulatory Gait and Fall Risk Assessment in the Wild (MAGFRA-W)) was acquired. The frames and image patches attributed to nine participants’ gait were annotated: (a) outdoor terrains: pavement (asphalt, cement, outdoor bricks/tiles), gravel, grass/foliage, soil, snow/slush; and (b) indoor terrains: high-friction materials (e.g., carpet, laminated floor), wood, and tiles. A series of ConvNets were developed: EgoPlaceNet categorizes frames into indoor and outdoor; and EgoTerrainNet (with outdoor and indoor versions) detects the enclosed terrain type in patches. To improve the framework’s generalizability, an independent training dataset with 9,424 samples was curated from different databases including GTOS and MINC-2500, and used for pretrained models’ (e.g., MobileNetV2) fine-tuning.

Results

EgoPlaceNet detected outdoor and indoor scenes in MAGFRA-W with 97.36$$\%$$
%
and 95.59$$\%$$
%
(leave-one-subject-out) accuracies, respectively. EgoTerrainNet-Indoor and -Outdoor achieved high detection accuracies for pavement (87.63$$\%$$
%
), foliage (91.24$$\%$$
%
), gravel (95.12$$\%$$
%
), and high-friction materials (95.02$$\%$$
%
), which indicate the models’ high generalizabiliy.

Conclusions

Encouraging results suggest that the integration of wearable cameras and deep learning approaches can provide objective contextual information in an automated manner, towards context-aware FLDBs for gait and fall risk assessment in the wild.
A preliminary study on the feasibility of community game-based respiratory muscle training for individuals with high cervical spinal cord injury levels: a novel approach
Authors: Kang Dongheon , Park Jiyoung , Eun Seon-Deok
Published: July 2022

Background

Respiratory disorders result in rehospitalization and premature death of patients with cervical spinal cord injuries (CSCI). Community game-based respiratory muscle training (RMT) programs could reduce secondary complications.

Methods

We examined the feasibility and preliminary efficacy of RMT as a community-based exercise program. Among the 10 included participants (eight male and two female), four, one, one, and four reported C3, C4, C5, and C6 complete injuries, respectively (eight graded by American Spinal Injury Association impairment scale [ASIA] A and two by ASIA B). Their mean age was 43 ± 12.3 y. The time since injury was 10 ± 6.7 y. The participants completed an RMT program for 60 min/day, twice weekly, for 8 weeks. The participants were trained in the use of a newly developed game-based RMT device. The device provides consistent pressure for respiratory muscle strength and endurance training. Seven RMT devices were modified to allow 10 game-based RMT programs. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), vital capacity (VC), inspiratory capacity (IC), inspiratory reserve volume (IRV), expiratory reserve volume (ERV), maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and peak cough flow (PCF) were measured.

Results

There were improvements after RMT compared to pre-RMT in FVC (p = 0.027, 10.62%, 0.22 effect size [ES]), PEF (p = 0.006, 23.21%, 0.45 ES), VC (p = 0.002, 35.52%, 0.60 ES), IC (p = 0.001, 46.94%, 0.81 ES), IRV (p = 0.001, 90.53%, 1.22 ES), MIP (p = 0.002, 97.25%, 1.32 ES), MEP (p = 0.005, 141.12%, 1.07 ES), and PCF (p = 0.001, 35.60%, 0.74 ES). The participants reported a positive impact of the program.

Conclusions

Community game-based RMT for individuals with CSCI appears to be safe and feasible. Community exercise with RMT use may have a positive impact on the respiratory measures for patients with CSCI who are vulnerable to respiratory compromise.

Trial registration

KCT0005980.
Machine intelligence-driven framework for optimized hit selection in virtual screening
Authors: Kumar Neeraj , Acharya Vishal
Published: July 2022

Virtual screening (VS) aids in prioritizing unknown bio-interactions between compounds and protein targets for empirical drug discovery. In standard VS exercise, roughly 10% of top-ranked molecules exhibit activity when examined in biochemical assays, which accounts for many false positive hits, making it an arduous task. Attempts for conquering false-hit rates were developed through either ligand-based or structure-based VS separately; however, nonetheless performed remarkably well. Here, we present an advanced VS framework—automated hit identification and optimization tool (A-HIOT)—comprises chemical space-driven stacked ensemble for identification and protein space-driven deep learning architectures for optimization of an array of specific hits for fixed protein receptors. A-HIOT implements numerous open-source algorithms intending to integrate chemical and protein space leading to a high-quality prediction. The optimized hits are the selective molecules which we retrieve after extreme refinement implying chemical space and protein space modules of A-HIOT. Using CXC chemokine receptor 4, we demonstrated the superior performance of A-HIOT for hit molecule identification and optimization with tenfold cross-validation accuracies of 94.8% and 81.9%, respectively. In comparison with other machine learning algorithms, A-HIOT achieved higher accuracies of 96.2% for hit identification and 89.9% for hit optimization on independent benchmark datasets for CXCR4 and 86.8% for hit identification and 90.2% for hit optimization on independent test dataset for androgen receptor (AR), thus, shows its generalizability and robustness. In conclusion, advantageous features impeded in A-HIOT is making a reliable approach for bridging the long-standing gap between ligand-based and structure-based VS in finding the optimized hits for the desired receptor. The complete resource (framework) code is available at https://gitlab.com/neeraj-24/A-HIOT.

Graphical Abstract
Single-cell RNA sequencing reveals the potential mechanism of heterogeneity of immunomodulatory properties of foreskin and umbilical cord mesenchymal stromal cells
Authors: Cai Siyu , Fan Chuiqin , Xie Lichun , Zhong Huifeng , Li Aijia , Lv Siyu , Liao Maochuan , Yang Xixi , Su Xing , Wang Yue , Wang Hongwu , Wang Manna , Huang Peng , Liu Yulin , Wang Yu , Liu Yufeng , Wang Tianyou , Zhong Yong , Ma Lian
Published: July 2022

Background

Mesenchymal stromal cells (MSCs) are heterogeneous populations. Heterogeneity exists within the same tissue and between different tissues. Some studies have found enormous heterogeneity in immunomodulatory function among MSCs derived from different tissues. Moreover, the underlying mechanism of heterogeneity in immunomodulatory abilities is still unclear.

Methods

Foreskin mesenchymal stromal cells (FSMSCs) and human umbilical cord mesenchymal stromal cells (HuMSCs) were isolated and cultured until the third passage. According to the International Association for Cell Therapy standard, we confirmed the cell type. Then, FSMSCs and HuMSCs were cocultured with human peripheral blood mononuclear cells (PBMCs) stimulated by lipopolysaccharide (LPS) in vitro. Furthermore, the supernatant was sampled for an enzyme-linked immunosorbent assay to investigate the secretion of IL-1β, IL-6, IL-10, TNF-α, and TGF-β1. Finally, we performed single-cell RNA sequencing (scRNA-seq) of FSMSCs and HuMSCs.

Results

We successfully identified FSMSCs and HuMSCs as MSCs. When cocultured with LPS pretreated PBMCs, FSMSCs and HuMSCs could effectively reduced the secretion of IL-1β and TNF-α. However, FSMSCs stimulated the PBMCs to secrete more IL-10, TGF-β1, and IL-6. Furthermore, 4 cell subsets were identified from integrated scRNA-seq data, including proliferative MSCs (MKI67+,CD146low+,NG2+,PDGFRB−), pericytes (CD146high+,PDGFRB+,MKI67−,CD31−,CD45−,CD34−), immune MSCs (CXCL12high+,PTGIShigh+,PDGFRB+,CD146−,MKI67−) and progenitor proliferative MSCs (CXCL12low+,PTGISlow+,PDGFRB+,CD146−,MKI67−). Among them, we found that immune MSCs with strengthened transcriptional activity were similar to pericytes with regard to the degree of differentiated. Various of immune-related genes, gene sets, and regulons were also enriched in immune MSCs. Moreover, immune MSCs were determined to be close to other cell subsets in cell–cell communication analysis. Finally, we found that the proportion of immune MSCs in foreskin tissue was highest when comparing the subset compositions of MSCs derived from different tissues.

Conclusions

FSMSCs show better immunomodulatory capacity than HuMSCs in vitro. Moreover, immune MSCs may play a vital role in the heterogeneity of immunoregulatory properties. This study provides new insights suggesting that immune MSCs can be isolated to exert stable immunoregulatory functions without being limited by the heterogeneity of MSCs derived from different tissues.