bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of habit formation interventions on physical activity habit strength: meta-analysis and meta-regression
Authors: Ma Haoming , Wang Aoqi , Pei Runyuan , Piao Meihua 
Published: September 2023

Abstract
Background
Interventions aimed at promoting physical activity (PA) behavior through habit formation pathways are gaining popularity, as they differ from conventional interventions that rely on intention pathways. Past research has established a positive correlation between PA habits and behavior. However, the efficacy of current interventions designed to form PA habits and improve PA automaticity is not yet fully ascertained. Additionally, the intervention components that significantly impact the effectiveness of these interventions are yet to be determined.

Methods
This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We conducted a search of three databases (PubMed, Embase, and Cochrane Library) from January 2000 to December 2022, with a focus on interventions for developing PA habits. Two independent authors conducted paper selection, quality assessment, data extraction, and coding of behavior change techniques (BCTs). The effect size of interventions was calculated using standardized mean difference. Subgroup analyses were carried out based on follow-up duration, delivery method, sample characteristics, and theory. Furthermore, we employed meta-regression to investigate the association between BCTs and PA habits.

Results
Ten eligible studies with relatively high quality were included in the final data set. Characteristics of studies varied in intervention sample and delivery way. The habit formation interventions significantly increased PA habit (SMD = 0.31, 95% CI 0.14—0.48, P < .001) compared to the control groups. Subgroup analysis demonstrated that the duration of follow-up ≤ 12 weeks have a higher effect size on PA habit than the duration > 12 weeks. Meta-regression revealed that problem solving has a significant positive association with effectiveness improvement (β = 0.36, 95% CI 0.17–0.55), while social reward is linked with a reduction in effectiveness (β = -0.40, 95% CI -0.74–0.06).

Conclusions
Our findings reveal that habit formation interventions are effective in fostering PA habit. Future studies could leverage the insights form this study to optimize the intervention design and achieve better effectiveness.
Enhanced systemic tumor suppression by in situ vaccine combining radiation and OX40 agonist with CpG therapy
Authors: Sun Zhichen , Chu Yanhong , Xiao Jie , Yang Yueling , Meng Fanyan , Wang Xinyue , Dong Yanbing , Zhu Junmeng , Wu Yirong , Qin Lanqun , Ke Yaohua , Liu Baorui , Liu Qin 
Published: September 2023

Abstract
Background
In situ tumor vaccine has been gradually becoming a hot research field for its advantage of achieving personalized tumor therapy without prior antigen identification. Various in situ tumor vaccine regimens have been reported to exert considerable antitumor efficacy in preclinical and clinical studies. However, the design of in situ tumor vaccines still needs further optimization and the underlying immune mechanism also waits for deeper investigation.

Methods
A novel triple in situ vaccine strategy that combining local radiation with intratumoral injection of TLR9 agonist CpG and OX40 agonist was established in this sturdy. Local and abscopal antitumor efficacy as well as survival benefit were evaluated in the bilateral tumors and pulmonary metastasis model of B16F10 melanoma. In situ vaccine-induced immune responses and immune-associated variation in tumor environment were further investigated using multiparameter flow cytometry and RNA sequencing. Base on the analysis, the RT + CpG + αOX40 triple in situ vaccine was combined with checkpoint blockade therapy to explore the potential synergistic antitumor efficacy.

Results
Enhanced tumor suppression was observed with minimal toxicity in both treated and untreated abscopal tumors after receiving RT + CpG + αOX40 triple vaccine. The introduction of local radiation and OX40 agonist benefit more to the inhibition of local and abscopal lesions respectively, which might be partially attributed to the increase of effector memory T cells in the tumor microenvironment. Further analysis implied that the triple in situ vaccine did not only activate the microenvironment of treated tumors, with the upregulation of multiple immune-associated pathways, but also enhanced systemic antitumor responses, thus achieved superior systemic tumor control and survival benefit. Moreover, the triple in situ vaccine synergized with checkpoint blockade therapy, and significantly improved the therapeutic effect of anti-programmed cell death protein (PD)-1 antibody.

Conclusion
This triple combining in situ vaccine induced intensive antitumor responses, mediated effective systemic tumor control and survival benefit, and displayed impressive synergistic antitumor effect with checkpoint blockade therapy. These data preliminary confirmed the efficacy, feasibility and safety of the triple combining in situ vaccine, suggesting its great application potential as both monotherapy and a part of combined immunotherapeutic regimens in clinical scenario.
The impact of the COVID-19 pandemic on patients with juvenile idiopathic inflammatory myopathies
Authors: Wahezi Dawn M. , Jerome Dominique , Rothschild Evin , Yi Belina , Dvergsten Jeffrey , Tarvin Stacey , Kim Susan , Rubinstein Tamar ,   for the CARRA JDM workgroup
Published: September 2023

Abstract
Background
Throughout the COVID-19 pandemic, there have been concerns regarding the risks of infection in patients with autoimmune disease. In this study, we investigated the impact of the pandemic on patients with juvenile idiopathic inflammatory myopathies (JIIM).

Methods
Data were collected using a patient/caregiver survey via Research Electronic Data Capture (REDCap) database. Eligibility included JIIM diagnosis and current age less than 21 years old. Surveys were distributed via the CureJM organization, social media, Childhood Arthritis and Rheumatology Research Alliance (CARRA) network and Dr. Peter Dent Pediatric Rheumatology Bulletin Board.

Results
Eighty-four respondents accessed the survey, 70 (83%) consented to participate, and 54 out of 70 completed the full survey (77%). Twenty-seven out of 57 patients (47%) tested positive for COVID-19, with 7 (12%) testing positive more than once. Despite broad usage of immunosuppressive medications, 24 out of 27 (89%) reported mild symptoms with none requiring hospitalization. Four patients reported a flare of JIIM symptoms after COVID-19; three of whom held immunomodulatory medications during their infection. Thirty-seven out of 54 respondents (69%) reported vaccination against COVID-19, with 9 out of 37 (24%) reporting minor vaccine side effects and one reporting JIIM flare post vaccination. Twenty-one out of 54 (39%) respondents reported psychosocial concerns related to the COVID-19 pandemic.

Conclusions
Patients with JIIM, including those on multiple immunosuppressive medications, had mild symptoms related to COVID-19. Most patients tolerated COVID-19 vaccination well. Few patients had disease flare post-COVID-19 or vaccination. Mental health concerns were demonstrated in JIIM patients during the COVID-19 pandemic.
Genital mycoplasma infection: a systematic review and meta-analysis
Authors: Cheng Chen , Chen Xiangyu , Song Yuxuan , Wang Shangren , Pan Yang , Niu Shuai , Wang Rui , Liu Li , Liu Xiaoqiang 
Published: September 2023

Abstract
Background
Recent studies have suggested that genital mycoplasma infections may be associated with male infertility. However, this association remains controversial due to time lapse, sample size, and regional prevalence.

Objectives
This study aimed to systematically evaluate the relationship between genital mycoplasma and male infertility through a meta-analysis and to provide a basis for the clinical management of male infertility.

Methods
We conducted a search on PubMed, EMBASE, the Cochrane Library, and CNKI databases, from January 2000 to June 2023 to identify case–control studies on the interrelationship between genital mycoplasma infection and male infertility. Two independent researchers performed an assessment of the methodological quality of trials according to the Newcastle–Ottawa scale and extracted data strictly based on the inclusion and exclusion criteria, and afterward, we carried out a meta-analysis using Stata 16.0. Pooled odds ratios (OR) with 95% confidence intervals (CI) were used to assess this relationship.

Results
This meta-analysis included 21 studies from seven countries with a total of 53025 infertility cases and 6435 controls; the age range of the participating men was from 20 to 59 years old. The results obtained showed a higher prevalence of M. genitalium, M. hominis and U. urealyticum infections in infertile men than in the controls, with the opposite result for U. parvum (M. genitalium, OR, 3.438 [95% CI: 1.780, 6.643], with P = 0.000; M. hominis, OR, 1.840 [95% CI: 1.013, 3.343], with P = 0.045; U. urealyticum, OR, 3.278 [95% CI: 2.075, 5.180], with P = 0.000; U. parvum, OR, 1.671 [95% CI: 0.947, 2.950], with P = 0.077). Further, two subgroup analyses also showed that M. hominis and U. urealyticum infections were strongly associated with male infertility in China (M. hominis, P = 0.009; U. urealyticum, P = 0.000); however, M. hominis and U. urealyticum infection was not strongly associated with male infertility worldwide (M. hominis, P = 0.553; U. urealyticum, P = 0.050).

Conclusion
This meta-analysis revealed that male infertility was significantly associated with M. genitalium, M. hominis and U. urealyticum infections, while U. parvum infection was not. Further, our study showed that genital mycoplasma infection influences male infertility and provides a basis for future treatment.
Effect of weight change on the association between overall and source of carbohydrate intake and risk of metabolic syndrome: Tehran lipid and glucose study
Authors: Hosseinpour-Niazi Somayeh , Bakhshi Bahar , Mirmiran Parvin , Gaeini Zahra , Hadaegh Farzad , Azizi Fereidoun 
Published: September 2023

Abstract
Background
In this prospective cohort study, we aimed to evaluate the association between dietary carbohydrates, whole grains, refined grains, and simple sugar with the risk of metabolic syndrome (MetS) and assess the effect of weight change on these associations.

Methods
This study was conducted within the framework of the Tehran Lipid and Glucose Study (TLGS). We included 1915 healthy participants with complete demographic, anthropometric and dietary measurements, among whom 591 developed MetS during 8.9 years of follow-up. Intake of dietary carbohydrates, whole grains, refined grains, and simple sugar was assessed with a validated semi-quantitative food frequency questionnaire. Multivariable adjusted Cox regression was used to estimate hazard ratios (HRs) for MetS events across tertiles of dietary variables. Using joint classification, the effect of weight change on the association between dietary variables and risk of MetS was assessed by Cox regression.

Results
Carbohydrate intake was not associated with the risk of MetS in multivariable-adjusted models. Whole grains intake was inversely associated with the risk of MetS (HR: 0.78, CI: 0.63–0.98), while this association disappeared after adjustment for weight change. The risk of MetS increased by 11% (1.11, 1.09–1.14) for each 3% energy increment from simple sugar, and by 5% (1.05, 1.03–1.08) for each 1 serving/day increment in refined grains. Consumption of refined grains increased the risk of MetS; an effect modification of this association was found by weight change. Among subjects with weight loss, intake of refined grains < median intake decreased the risk of MetS (0.59, 0.41–0.87). However, consumption of refined grains ≥ median intake increased the risk of MetS in individuals with weight gain (1.47, 1.08–2.01). Simple sugar was positively associated with an increased risk of MetS, after adjustment for weight change (3.00, 2.37–3.82). In joint classification, intake of simple sugar greater than median intake increased the risk of MetS, independent of weight change.

Conclusion
Our findings suggest an effect modification by weight change on the association between carbohydrates, and refined grains intake and the risk of MetS. Weight loss along with lower consumption of carbohydrates, and refined grains reduced the risk of MetS. However, simple sugar intake, regardless of weight change, was associated with an increased risk of MetS.
Metformin increases the expression of proinflammatory cytokines and inhibits supraspinatus fatty infiltration
Authors: Yoon Jong Pil , Park Sung-Jin , Kim Dong-Hyun , Chung Seok Won 
Published: September 2023

Abstract
Background
After a rotator cuff (RC) tendon tear, the supraspinatus (SS) inflammatory response induces fatty infiltration (FI). Metformin has the effect of regulating the initial inflammatory response of atrophic muscles. Therefore, this study aimed to investigate the effect of metformin use on modulating the expression of proinflammatory cytokines and SS FI in an acute RC tear rat model.

Methods
This study used 26 male Sprague–Dawley rats. Animals were randomly divided into two groups: The metformin group received metformin for 5 days after cutting the RC tendon, and the control group was administered only with saline after cutting the tendon. Metformin 50 mg/kg was intraperitoneally injected for 5 days. Three rats in each group were sacrificed 5 days after SS tendon rupture surgery, and 10 rats in each group were sacrificed 14 days after surgery. The SS was sampled 5 days after SS tendon tear surgery, and the expression of proinflammatory cytokines was measured by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). On day 14 after sampling, histological analysis of the SS was performed using hematoxylin and eosin, Masson’s trichrome, and picrosirius red staining.

Results
On day 5 of surgery, the expression values of interferon gamma (increased 7.2-fold, P < .01), tumor necrosis factor alpha (increased 13-fold, P < .05), interleukin-1β (increased 4.7-fold, P < .001), and interleukin-6 (increased 4.6-fold, P < .01) increased significantly in the metformin group compared with those in the control group. As a result of Oil Red O staining, SS FI was significantly suppressed in the metformin group compared with that in the control group (metformin group, 305 ± 50.3 µm2, P < .001; control group, 3136 ± 662.8 µm2, P < .001). In addition, the SS volume of the metformin group was not reduced compared with those of the control group, and the morphology and structure of the SS were better preserved.

Conclusions
The results of this study revealed that metformin can increase the expression of proinflammatory cytokines and suppress SS fat infiltration in delayed sutures.
Jian Yun Qing Hua Decoction inhibits malignant behaviors of gastric carcinoma cells via COL12A1 mediated ferroptosis signal pathway
Authors: Liu Baoxinzi , Li Yu , Xu Yuanyuan , Xue Weiwei , Jin Zhichao 
Published: September 2023

Abstract
Background
Jian Yun Qing Hua Decoction (JYQHD), a traditional Chinese medicine decoction, which has been applied in the treatment of gastric cancer (GC). We attempt to confirm the anti-gastric cancer effect of JYQHD and explore the mechanism of JYQHD.

Methods
Acute toxicity test was used to understand the toxicity of JYQHD. We studied the expression and prognostic outcome of COL12A1 within GC tissues through the network databases. Using several web-based databases, we analyzed the major components and targets of JYQHD, as well as known therapeutic targets in gastric cancer. The Venn diagram was utilized to obtain the overlapped genes. Lentiviral vector, shRNAs and plasmids, were used to transfect GC cells. Cell counting kit-8 (CCK8), sphere formation, malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS), Fe2+, transmission electron microscopy (TEM), quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), Western-Blot (WB), and immunohistochemical (IHC) assays were employed to investigate the role and mechanism of COL12A1 and JYQHD in GC.

Results
The results showed that JYQHD was non-toxic and safe. JYQHD inhibited growth and sphere formation ability through inducing the ferroptosis of GC cells, and suppressed the GC cells induced subcutaneous xenograft tumor growth. COL12A1 was highly expressed in gastric cancer tissues, indicating poor prognosis. COL12A1 specifically enhanced GC cell progression and stemness via suppressing ferroptosis. JYQHD down-regulated COL12A1 in order to suppress the stemness of GC cells via inducing ferroptosis.

Conclusion
COL12A1 inhibited ferroptosis and enhanced stemness in GC cells. JYQHD inhibited the development of GC cells by inhibiting cancer cell stemness via the ferroptosis pathway mediated by COL12A1.
Financing repurposed drugs for rare diseases: a case study of Unravel Biosciences
Authors: Abouarab Bechara , Bazarian Christian , Ben Chaouch Zied , Lo Andrew W. , Mourenza Gonzalez Guillermo , Novak Richard , Vigneault Frederic 
Published: September 2023

Abstract
Background
We consider two key challenges that early-stage biotechnology firms face in developing a sustainable financing strategy and a sustainable business model: developing a valuation model for drug compounds, and choosing an appropriate operating model and corporate structure. We use the specific example of Unravel Biosciences—a therapeutics platform company that identifies novel drug targets through off-target mechanisms of existing drugs and then develops optimized new molecules—throughout the paper and explore a specific scenario of drug repurposing for rare genetic diseases.

Results
The first challenge consists of producing a realistic financial valuation of a potential rare disease repurposed drug compound, in this case targeting Rett syndrome. More generally, we develop a framework to value a portfolio of pairwise correlated rare disease compounds in early-stage development and quantify its risk profile. We estimate the probability of a negative return to be $$80.8\%$$

80.8
%

for a single compound and $$56.1\%$$

56.1
%

for a portfolio of 8 drugs. The probability of selling the project at a loss decreases from $$79.2\%$$

79.2
%

(phase 3) for a single compound to $$55.4\%$$

55.4
%

(phase 3) for the 8-drug portfolio. For the second challenge, we find that the choice of operating model and corporate structure is crucial for early-stage biotech startups and illustrate this point with three concrete examples.

Conclusions
Repurposing existing compounds offers important advantages that could help early-stage biotech startups better align their business and financing issues with their scientific and medical objectives, enter a space that is not occupied by large pharmaceutical companies, and accelerate the validation of their drug development platform.
Gastrointestinal involvement in Klippel-Trénaunay syndrome: pathophysiology, evaluation, and management
Authors: Wang Huaijie , Lin Weilong , Xie Chong , Yang Weijia , Zhou Jinbang , Guo Zhengtuan 
Published: September 2023

AbstractKlippel-Trénaunay syndrome is typically a complex combined capillary-lymphatic-venous malformation in lower limb. Gastrointestinal involvement is not infrequent in Klippel-Trénaunay syndrome. Rectal bleeding is the most common complication. In recent years, this condition has been increasingly reported. However, most authors simply described extreme manifestations or various combinations of clinical observations. The underlying pathophysiology of gastrointestinal involvement in Klippel-Trénaunay syndrome has been underrecognized. Pathophysiologically, some seemingly adequate managements are pitfalls in treatment. Anorectosigmoid vascular malformations in KTS have distinct and more complicated pathophysiologies than anorectal vascular malformation. Once understanding the pathophysiology, some patients can be successfully managed with a staged plan in our practice. Therefore, recognizing the pathophysiologies of gastrointestinal involvement is needed to evaluate, prevent pitfalls, and determine adequate managements for practitioners. Because of the complexity and rarity of this condition, prospective controlled study or a large cohort of patients is impossible. Based on literature review and our practice, we discuss pathophysiologies, evaluation, pitfalls, and treatment strategies for gastrointestinal involvement in Klippel-Trénaunay syndrome.
Pre-hospital endotracheal intubation in severe traumatic brain injury: ventilation targets and mortality—a retrospective analysis of 308 patients
Authors: Knapp Jürgen , Doppmann Pascal , Huber Markus , Meuli Lorenz , Albrecht Roland , Sollid Stephen , Pietsch Urs 
Published: September 2023

Abstract
Background
Traumatic brain injury (TBI) remains one of the main causes of mortality and long-term disability worldwide. Maintaining physiology of brain tissue to the greatest extent possible through optimal management of blood pressure, airway, ventilation, and oxygenation, improves patient outcome. We studied the quality of prehospital care in severe TBI patients by analyzing adherence to recommended target ranges for ventilation and blood pressure, prehospital time expenditure, and their effect on mortality, as well as quality of prehospital ventilation assessed by arterial partial pressure of CO2 (PaCO2) at hospital admission.

Methods
This is a retrospective cohort study of all TBI patients requiring tracheal intubation on scene who were transported to one of two major level 1 trauma centers in Switzerland between January 2014 and December 2019 by Swiss Air Rescue (Rega). We assessed systolic blood pressure (SBP), end-tidal partial pressure of CO2 (PetCO2), and PaCO2 at hospital admission as well as prehospital and on-scene time. Quality markers of prehospital care (PetCO2, SBP, prehospital times) and prehospital ventilation (PaCO2) are presented as descriptive analysis. Effect on mortality was calculated by multivariable regression analysis and a logistic general additive model.

Results
Of 557 patients after exclusions, 308 were analyzed. Adherence to blood pressure recommendations was 89%. According to PetCO2, 45% were normoventilated, and 29% had a SBP ≥ 90 mm Hg and were normoventilated. Due to the poor correlation between PaCO2 and PetCO2, only 33% were normocapnic at hospital admission. Normocapnia at hospital admission was strongly associated with reduced probability of mortality. Prehospital and on-scene times had no impact on mortality.

Conclusions
PaCO2 at hospital admission is strongly associated with mortality risk, but normocapnia is achieved only in a minority of patients. Therefore, the time required for placement of an arterial cannula and prehospital blood gas analysis may be warranted in severe TBI patients requiring on-scene tracheal intubation.