bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the COVID-19 pandemic on the development of locomotive syndrome
Authors: Terai Hidetomi , Hori Yusuke , Takahashi Shinji , Tamai Koji , Iwamae Masayoshi , Hoshino Masatoshi , Ohyama Shoichiro , Yabu Akito , Nakamura Hiroaki 
Published: December 2021

Background The coronavirus disease 2019 (COVID-19) pandemic has affected people in various ways, including restricting their mobility and depriving them of exercise opportunities. Such circumstances can trigger locomotor deterioration and impairment, which is known as locomotive syndrome. The purpose of this study was to investigate the incidence of locomotive syndrome in the pandemic and to identify its risk factors. Methods: This was a multicenter questionnaire survey performed between 1 November 2020 and 31 December 2020 in Japan. Patients who visited the orthopedics clinic were asked to answer a questionnaire about their symptoms, exercise habits, and locomotor function at two time points, namely, pre-pandemic and post-second wave (current). The incidence of locomotive syndrome in the COVID-19 pandemic was investigated. Additionally, multiple logistic regression analysis was used to identify the risk factors for developing locomotive syndrome during the pandemic. Results: A total of 2829 patients were enrolled in this study (average age: 61.1 ± 17.1 years; 1532 women). The prevalence of locomotive syndrome was 30% pre-pandemic, which increased significantly to 50% intra-pandemic. Among the patients with no symptoms of locomotive syndrome, 30% developed it in the wake of the pandemic. In the multinomial logistic regression analysis, older age, deteriorated or newly occurring symptoms of musculoskeletal disorders, complaints about the spine or hip/knee joints, and no or decreased exercise habits were independent risk factors for developing locomotive syndrome. Conclusions: The prevalence of locomotive syndrome in patients with musculoskeletal disorders has increased during the COVID-19 pandemic. In addition to age, locomotor symptoms, especially spine or hip/knee joint complaints, and exercise habits were associated with the development of locomotive syndrome. Although the control of infection is a priority, the treatment of musculoskeletal disorders and ensuring exercise habits are also essential issues to address during a pandemic such as COVID-19.
Off to a Jump Start: Using Immersive Activities to Integrate Continuity Clinic and Advocacy
Authors: Sieplinga Kira , Disbrow Emily , Triemstra Justin , van de Ridder Monica 
Published: December 2021

BACKGROUND Training in advocacy is an important component of graduate medical education. Several models have been implemented by residency programs to address this objective. Little has been published regarding application of immersive advocacy activities integrated into continuity clinic. OBJECTIVE To create an Integrated Community Health and Child Advocacy Curriculum (ICHCA) by integrating advocacy activities that were immersive and contextualized in a continuity clinic setting and to familiarize interns with continuity clinic immediately at the beginning of their training. METHODS We utilized a socio-constructivist lens, Kern's Six-step curriculum development and a published curriculum mapping tool to create the curriculum. Twenty residents completed ICHCA in 2019. Evaluations from key stakeholders including participants, support staff and attendings were analyzed on four levels of Kirkpatrick's model. We compared results before intervention, immediately following intervention and ten months following intervention. RESULTS We demonstrated improvement in learner satisfaction, knowledge and behaviors with respect to advocacy in the clinical environment. Response rate was 70% (7/10) for attendings, 75% for support staff (15/20) and 72.5% for residents (29/40). Our intervention was feasible, no cost, and required no additional materials or training as it relied on learning in real time. CONCLUSIONS An integrated advocacy curriculum utilizing the mapping tool for curricular design and evaluation is feasible and has value demonstrated by improvements in reaction, knowledge, and behaviors. This model improves understanding of social responsibility and can be implemented similarly in other residency programs.
MLSA phylogeny and antimicrobial susceptibility of clinical Nocardia isolates: a multicenter retrospective study in China
Authors: Wei Ming , Xu Xinmin , Yang Jingxian , Wang Peng , Liu Yongzhe , Wang Shuai , Yang Chunxia , Gu Li 
Published: December 2021

Abstract
Background
With the increase of detection rate and long treatment period, nocardiosis has become a noticeable problem in China. However, there are limited large-scale studies on the epidemiology and antimicrobial susceptibility profiles of clinical Nocardia spp. in China. The present study aimed to explore the species distribution and drug susceptibility pattern of 82 clinical Nocardia isolates from three tertiary hospitals in China by multilocus sequence analysis (MLSA) and broth microdilution (BMD) method.

Results
Pulmonary nocardiosis (90.2%) was the most common clinical presentation of infection. N. cyriacigeorgica (n = 33; 40.2%) and N. farcinica (n = 20; 24.4%) were the most frequently encountered Nocardia species, followed by N. otitidiscaviarum (n = 7; 8.5%), N. abscessus (n = 5; 6.1%), N. asiatica (n = 4; 4.9%), and N. wallacei (n = 4; 4.9%). Trimethoprim/sulfamethoxazole (SXT) remained high activity against all Nocardia isolates (susceptibility rate: 98.8%). Linezolid and amikacin were also highly active; 100 and 95.1% of all isolates demonstrated susceptibility, respectively. Except for N. otitidiscaviarum, all the Nocardia isolates exhibited high susceptibility rates to imipenem. The resistance rates of all isolates to clarithromycin and ciprofloxacin were 92.7 and 73.2%, respectively, but the resistance rate of N. farcinica to ciprofloxacin was only 25%.

Conclusions
The clinically isolated Nocardia spp. had diverse antimicrobial susceptibility patterns, which were similar to the reports by other groups elsewhere, but some differences were also observed, mainly including imipenem and ciprofloxacin. According to this study, SXT still can be the first choice for empirical therapy due to the low resistance rate. Linezolid can be chosen when a patient is allergic to SXT, and amikacin and imipenem can be the choice in a combination regimen.
Observational study on fluid therapy management in surgical adult patients
Authors: Colomina Maria J. , Ripollés-Melchor Javier , Guilabert Patricia , Jover José Luis , Basora Misericordia , Cassinello Concha , Ferrandis Raquel , Llau Juan V. , Peñafiel Judith 
Published: December 2021

Abstract
Background
Perioperative fluid therapy management is changing due to the incorporation of different fluids, surgical techniques, and minimally invasive monitoring systems. The objective of this study was to explore fluid therapy management during the perioperative period in our country.

Methods
We designed the Fluid Day study as a cross-sectional, multicentre, observational study. The study was performed in 131 Spanish hospitals in February 2019. We included adult patients undergoing general anaesthesia for either elective or non-elective surgery. Demographic variables were recorded, as well as the type and total volume of fluid administered during the perioperative period and the monitorization used. To perform the analysis, patients were categorized by risk group.

Results
We recruited 7291 patients, 6314 of which were included in the analysis; 1541 (24.4%) patients underwent high-risk surgery, 1497 (23. 7%) were high risk patients, and 554 (8.7%) were high-risk patients and underwent high-risk surgery; 98% patients received crystalloids (80% balanced solutions); intraoperative colloids were used in 466 patients (7.51%). The hourly intraoperative volume in mL/kg/h and the median [Q1; Q3] administered volume (mL/kg) were, respectively, 6.67 [3.83; 8.17] ml/Kg/h and 13.9 [9.52;5.20] ml/Kg in low-risk patients undergoing low- or intermediate-risk surgery, 6 [4.04; 9.08] ml/Kg/h and 15.7 [10.4;24.5] ml/Kg in high- risk patients undergoing low or intermediate-risk surgery, 6.41 [4.36; 9.33] ml/Kg/h and 20.2 [13.3;32.4] ml/Kg in low-risk patients undergoing high-risk surgery, and 5.46 [3.83; 8.17] ml/Kg/h and 22.7[14.1;40.9] ml/Kg in high-risk patients undergoing high- risk surgery . We used advanced fluid monitoring strategies in 5% of patients in the intraoperative period and in 10% in the postoperative period.

Conclusions
The most widely used fluid was balanced crystalloids. Colloids were used in a small number of patients. Hourly surgery volume tended to be more restrictive in high-risk patients but confirms a high degree of variation in the perioperatively administered volume. Scarce monitorization was observed in fluid therapy management.

Trial registration
Clinical Trials: NCT03630744.
An adaptive gBOIN design with shrinkage boundaries for phase I dose-finding trials
Authors: Mu Rongji , Hu Zongliang , Xu Guoying , Pan Haitao 
Published: December 2021

Abstract
Background
With the emergence of molecularly targeted agents and immunotherapies, the landscape of phase I trials in oncology has been changed. Though these new therapeutic agents are very likely induce multiple low- or moderate-grade toxicities instead of DLT, most of the existing phase I trial designs account for the binary toxicity outcomes. Motivated by a pediatric phase I trial of solid tumor with a continuous outcome, we propose an adaptive generalized Bayesian optimal interval design with shrinkage boundaries, gBOINS, which can account for continuous, toxicity grades endpoints and regard the conventional binary endpoint as a special case.

Result
The proposed gBOINS design enjoys convergence properties, e.g., the induced interval shrinks to the toxicity target and the recommended dose converges to the true maximum tolerated dose with increased sample size.

Conclusion
The proposed gBOINS design is transparent and simple to implement. We show that the gBOINS design has the desirable finite property of coherence and large-sample property of consistency. Numerical studies show that the proposed gBOINS design yields good performance and is comparable with or superior to the competing design.
The association between living environmental factors and adolescents’ body weight: a cross-sectional study
Authors: Huang Siyi , Sha Sha , Du Wei , Zhang Hanwen , Wu Xinyi , Jiang Chongmin , Zhao Yan , Yang Jie 
Published: December 2021

Abstract
Background
The effect of the living environment on public health has received increasingly scholarly attention. This study aims to explore the relationship between adolescents’ body weight and their living environmental factors.

Methods
This cross-sectional study comprised 1362 middle-school students from Nanjing and 826 from Changzhou in China. We further collected information on living environmental factors based on their home address and ran multivariate logistic regressions to explore potential correlations after considering a range of potential confounding factors.

Results
Approximately 25% (n = 303) of students from Nanjing and 26% (n = 205) of students from Changzhou were excessive body weight. In Nanjing, students’ BMI (Body Mass Index) showed a strong negative correlation with the number of sports venues in their neighborhood (Adjusted Odds Ratio (AOR): 0.64, 95%CI: 0.40–0.94) after controlling for other covariates. In Changzhou, we observed a positive correlation between adolescents’ body weight and the number of bus stops in their neighbourhood (AOR:1.63, 95%CI:1.11–2.38).

Conclusions
The living environment factors were independently associated with teenagers’ excessive body weight. We hypothesis that the environmental risk factors might be associated with political management, which will consequently affect personal health outcomes. Further research and proactive measures are required to manage those potential risks and attenuate the problem.
Personalized neoantigen vaccine prevents postoperative recurrence in hepatocellular carcinoma patients with vascular invasion
Authors: Cai Zhixiong , Su Xiaoping , Qiu Liman , Li Zhenli , Li Xiaolou , Dong Xiuqing , Wei Fuqun , Zhou Yang , Luo Liuping , Chen Geng , Chen Hengkai , Wang Yingchao , Zeng Yongyi , Liu Xiaolong 
Published: December 2021

AbstractBackgroundClinically, prophylactic anti-recurrence treatments for hepatocellular carcinoma (HCC) patients after radical surgery are extremely limited. Neoantigen based vaccine can generate robust anti-tumor immune response in several solid tumors but whether it could induce anti-tumor immune response in HCC and serve as a safe and effective prophylactic strategy for preventing postoperative HCC recurrence still remain largely unclear.MethodsPersonalized neoantigen vaccine was designed and immunized for 10 HCC patients with high risk of postoperative recurrence in a prime-boost schedule. The safety and immune response were assessed through adverse events, tissue sequencing, ELISpot, TCR sequencing. The clinical response was evaluated by recurrence-free survival (RFS) and personalized circulating tumor DNA (ctDNA) sequencing.ResultsIn the 10 enrolled patients, no obvious adverse events were observed during neoantigen vaccinations. Until the deadline of clinical trial, 8 of 10 patients were confirmed with clinical relapse by imaging, the other 2 patients remained relapse-free. From receiving first neoantigen vaccination, the median RFS of 10 patients were 7.4 months. Among 7 patients received all planned neoantigen vaccinations, 5 of them demonstrated neoantigen-induced T cell responses and have significantly longer RFS after radical surgery than other 5 patients without responsive neoantigens or only with prime vaccination and propensity scores matching control patients (p = 0.035). Moreover, tracking personalized neoantigen mutations in ctDNA could provide real-time evaluation of clinical response in HCC patients during neoantigen vaccination and follow up.ConclusionPersonalized neoantigen vaccine is proved as a safe, feasible and effective strategy for HCC anti-recurrence, and its progression could be sensitively monitored by corresponding neoantigen mutations in ctDNA, and thus provided solid information for individualized medicine in HCC.Trial registrationThis study was registered at Chinese Clinical Trial Registry; Registration number:ChiCTR1900020990.
A novel biomimetic nanomedicine system with anti-inflammatory and anti-osteoporosis effects improves the therapy efficacy of steroid-resistant nephrotic syndrome
Authors: Li Jian , Zhao Mingyi , Xiang Xinying , He Qingnan , Gui Rong 
Published: December 2021

AbstractClinically, steroid-resistant nephrotic syndrome (SRNS) is always prolonged and difficult to treat and easily develops into end-stage renal disease, resulting in a low survival rate. Strategies to reverse steroid resistance and reduce the long-term use of high doses of steroid medicines are urgently needed. In this study, a novel nanoparticle drug system (Pm-GCH) with a core–shell structure was designed. Metal–organic frameworks, synthesized by glycyrrhizic acid (G) and calcium ions (Ca2+) loaded with hydrocortisone (H) were the core of the nanoparticles. Platelet membrane vesicles were the shells. The natural platelet membrane endows Pm-GCH with good biocompatibility and the ability to promote immune escape. In addition, under the chemotaxis of inflammatory factors, platelet membranes assist Pm-GCH in nonspecific targeting of the inflammatory sites of the kidney. Under an inflammatory acid environment, GCH slowly degrades and releases glycyrrhizic acid and hydrocortisone. Glycyrrhizic acid inhibits the inactivation of hydrocortisone, jointly inhibits the activity of phospholipase A2 (PLA2) and the classic activation pathway of complement C2, blocks the production of inflammatory factors, plays an anti-inflammatory role, and enhances the efficacy of hydrocortisone in the treatment of SRNS. Moreover, glycyrrhizic acid alleviates osteoporosis induced by long-term use of glucocorticoids. These results indicate that Pm-GCH is a promising treatment strategy for SRNS.Graphical Abstract
Lung histopathologic clusters in severe COVID-19: a link between clinical picture and tissue damage
Authors: Wu Maddalena Alessandra , Lopez Gianluca , Nebuloni Manuela , Ottolina Davide , Montomoli Jonathan , Carsana Luca , Fossali Tommaso , Castelli Antonio , Rech Roberto , Cogliati Chiara , Catena Emanuele , Colombo Riccardo 
Published: December 2021

Abstract
Background
Autoptic pulmonary findings have been described in severe COVID-19 patients, but evidence regarding the correlation between clinical picture and lung histopathologic patterns is still weak.

Methods
This was a retrospective cohort observational study conducted at the referral center for infectious diseases in northern Italy. Full lung autoptic findings and clinical data of patients who died from COVID-19 were analyzed. Lung histopathologic patterns were scored according to the extent of tissue damage. To consider coexisting histopathologic patterns, hierarchical clustering of histopathologic findings was applied.

Results
Whole pulmonary examination was available in 75 out of 92 full autopsies. Forty-eight hospitalized patients (64%), 44 from ICU and four from the medical ward, had complete clinical data. The histopathologic patterns had a time-dependent distribution with considerable overlap among patterns. Duration of positive-pressure ventilation (p < 0.0001), mean positive end-expiratory pressure (PEEP) (p = 0.007), worst serum albumin (p = 0.017), interleukin 6 (p = 0.047), and kidney SOFA (p = 0.001) differed among histopathologic clusters. The amount of PEEP for long-lasting ventilatory treatment was associated with the cluster showing the largest areas of early and late proliferative diffuse alveolar damage. No pharmacologic interventions or comorbidities affected the lung histopathology.

Conclusions
Our study draws a comprehensive link between the clinical and pulmonary histopathologic findings in a large cohort of COVID-19 patients. These results highlight that the positive end-expiratory pressures and the duration of the ventilatory treatment correlate with lung histopathologic patterns, providing new clues to the knowledge of the pathophysiology of severe SARS-CoV-2 pneumonia.
Childhood diagnoses in individuals identified as autistics in adulthood
Authors: Rødgaard Eya-Mist , Jensen Kristian , Miskowiak Kamilla Woznica , Mottron Laurent 
Published: December 2021

Abstract
Background
Autism is a developmental condition, where symptoms are expected to occur in childhood, but a significant number of individuals are diagnosed with autism for the first time in adulthood. Here, we examine diagnoses given in childhood among individuals that are diagnosed with autism in adulthood, to investigate whether the late autism diagnosis might be explained by misdiagnosis in childhood or diagnostic overshadowing.

Methods
Through the Danish National Patient Registry, we identified individuals diagnosed with autism in adulthood (N = 2199), as well as a control sample with no records of an autism diagnosis (N = 460,798) and calculated how many had received different psychiatric or neurological diagnoses in childhood.

Results
We found that most childhood diagnoses were overrepresented in those with an adult autism diagnosis, and attention-deficit hyperactivity disorder, affective disorders, anxiety, and stress disorders were the most prevalent childhood conditions in this group. However, 69% of males and 61% of females with adult autism diagnoses were not found to have received any of the investigated diagnoses before 18 years of age, and most childhood diagnoses were given after the age of 12.

Limitations
Milder to moderate cases of psychiatric conditions that have been solely treated by family physicians or school psychologists may not be fully included in our dataset. The study is based on data from the Danish health care system, and further research is needed to assess whether the findings can be generalized to other countries.

Conclusion
A majority of those with an adult autism diagnosis had no records of having received any of the investigated diagnoses in childhood. In these cases, the late autism diagnosis is therefore unlikely to be explained by either misdiagnosis or overshadowing. This result is at odds with the prevailing notion that autistic symptoms tend to diminish with age. Therefore, further research is warranted to examine how and if early signs of autism may have manifested among these individuals, and how similar they are to autistic people diagnosed earlier in their development.
A management model for admission and treatment of pediatric trauma cases
Authors: Tashlizky Madar Raya , Goldberg Avishay , Newman Nitza , Waisman Yehezkel , Greenberg David , Adini Bruria 
Published: December 2021

Abstract
Background
Pediatric trauma, particularly major trauma cases, are often treated in less than optimal facilities by providers who lack training and experience in treating severely injured children. We aimed to develop a management model for admission and treatment of pediatric trauma using the Theory of Constraints (TOC).

Methods
We conducted interviews with 17 highly experienced policy makers, senior nursing managers and medical managers in pediatrics and trauma. The interviews were analyzed by qualitative methods. The TOC was utilized to identify undesirable effects (UDEs) and core challenges, and to design a focused current reality tree (CRT). Subsequently, a management model for optimal admission and treatment of pediatric trauma was constructed.

Results
The CRT was illustrated according to 4 identified UDEs focusing on lack of: (1) clear definitions of case manager in pediatric trauma; (2) uniform criteria regarding the appropriate site for admitting pediatric trauma, (3) standard guidelines and protocols for treatment of trauma cases and for training of trauma medical teams; and (4) standard guidelines for evacuating pediatric trauma patients. The management model for treatment and admission of pediatric trauma is based on 3 major elements: human resources, hospital policy concerning the appropriate emergency department (ED) for pediatric trauma patients and clear definitions regarding children and trauma levels. Each of the elements contains components that should be clearly defined in order for a medical center to be designated for admitting and treating pediatric trauma patients.

Conclusions
Our analysis suggests that the optimal ED for pediatric trauma cases is one with available operating rooms, intensive care beds, an imaging unit, laboratories and equipment suitable for treating children as well as with staff trained to treat children with trauma. To achieve optimal outcomes, medical centers in Israel should be classified according to their trauma treatment capabilities and their ability to treat varied severities of pediatric trauma cases.