bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective association between phthalate exposure in childhood and liver function in adolescence: the Ewha Birth and Growth Cohort Study
Authors: Lee Seonhwa , Lee Hye Ah , Park Bohyun , Han Hyejin , Hong Young Sun , Ha Eun Hee , Park Hyesook
Published: January 2023

Background

Phthalate exposure is ubiquitous due to the widespread use of plastic products in daily life, and affects several health outcomes, including metabolic diseases. In this study, we evaluated the effects of phthalate exposure in childhood on liver function in adolescence. 

Methods

Among 164 Ewha Birth and Growth Cohort Study participants followed up during two exposure periods (when the children were aged 3–5 and 7–9 years), 126 were followed up at age 10–15 years. To investigate the relationship between phthalate exposure during the two periods and liver enzyme levels (ALT, AST, γ-GTP) in adolescence, differences between groups and the dose–response relationship were analyzed. In addition, we investigated differences in liver enzymes between groups based on the combined exposure levels (high or low) during the two periods. The interaction effect between phthalates and BMI on liver enzyme levels was evaluated, stratified by sex. 

Results

In the 3–5 year-old exposure period, ALT levels tended to increase as MECPP levels increased, while γ-GTP levels tended to increase as MiBP, MnBP, and ∑DBP levels increased. In addition, the group exposed to consistently high levels of phthalates at both time points had higher liver enzyme levels compared to the group that had lower exposure. In particular, the interaction effect between some phthalate metabolites and BMI in 3–5 year olds affected AST and γ-GTP levels in adolescence only in girls.

Conclusions

Exposure to phthalates in daily life during childhood affects liver enzyme levels in adolescence. Elevated liver enzyme levels are associated with the development of metabolic syndrome, implying that attention should be paid to phthalate exposure during childhood.
Fatty acid-binding protein-4 (FABP4) and matrix metalloproteinase-9 (MMP9) as predictive values for nonalcoholic steatohepatitis (NASH)
Authors: Wagner Jonas , Kumar Yogesh , Lautenbach Anne , von Kroge Philipp , Wolter Stefan , Mann Oliver , Izbicki Jakob , Gagliani Nicola , Duprée Anna
Published: January 2023

Background

Nonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis (NASH) increases the risk for liver cirrhosis. Noninvasive tests for NAFLD/NASH exist, but they are unreliable and thus liver biopsy remains the standard for diagnosis and new noninvasive diagnostic approaches are of great interest. The aim of this study was to test whether the serum levels of fatty acid-binding protein-4 (FABP4) and matrix metalloproteinase-9 (MMP9) could be used as a diagnostic tool for NASH.

Methods

Patients who underwent bariatric surgery and simultaneous liver biopsy were identified. Biopsies were assigned a NAFLD activity score (NAS). MMP9- and FABP4- Enzyme-linked Immunosorbent Assays (ELISAs) on serum samples were performed. The serum levels of FABP4/MMP9 were compared and different models to predict NASH were developed.

Results

A total of 84 patients were included, 28 patients (33.3%) were diagnosed with NASH. Higher concentrations of MMP9 in NASH patients (p < 0.01) were detected. FABP4 concentrations were not significantly increased. A moderate correlation between the NAS and MMP9 concentrations (r = 0.32, P < 0.01) was observed. The neural network model fit best with the dataset, with an area under the curve (AUC) of 83% and an accuracy of 88%.

Conclusion

Serum MMP9 levels are increased in patients with NASH and should routinely be measured in patients with obesity, but further investigations are needed to improve noninvasive NASH diagnosis.
PDGFB-targeted functional MRI nanoswitch for activatable T1–T2 dual-modal ultra-sensitive diagnosis of cancer
Authors: Zhang Ya’nan , Liu Lu , Li Wenling , Zhang Caiyun , Song Tianwei , Wang Peng , Sun Daxi , Huang Xiaodan , Qin Xia , Ran Lang , Tian Geng , Qian Junchao , Zhang Guilong
Published: January 2023

As one of the most significant imaging modalities currently available, magnetic resonance imaging (MRI) has been extensively utilized for clinically accurate cancer diagnosis. However, low signal-to-noise ratio (SNR) and low specificity for tumors continue to pose significant challenges. Inspired by the distance-dependent magnetic resonance tuning (MRET) phenomenon, the tumor microenvironment (TME)-activated off–on T1–T2 dual-mode MRI nanoswitch is presented in the current study to realize the sensitive early diagnosis of tumors. The tumor-specific nanoswitch is designed and manufactured on the basis of PDGFB-conjugating ferroferric oxide coated by Mn-doped silica (PDGFB-FMS), which can be degraded under the high-concentration GSH and low pH in TME to activate the T1–T2 dual-mode MRI signals. The tumor-specific off–on dual-mode MRI nanoswitch can significantly improve the SNR and is used successfully for the accurate diagnosis of early-stage tumors, particularly for orthotopic prostate cancer. In addition, the systemic delivery of the nanoswitch did not cause blood or tissue damage, and it can be excreted out of the body in a timely manner, demonstrating excellent biosafety. Overall, the strategy is a significant step in the direction of designing off–on dual-mode MRI nanoprobes to improve imaging accuracy, which opens up new avenues for the development of new MRI probes.
PHF5A facilitates the development and progression of gastric cancer through SKP2-mediated stabilization of FOS
Authors: Zhang Zhandong , Peng Liangqun , Yang Wei , Li Baodong , Hua Yawei , Luo Suxia
Published: January 2023

Background

Gastric cancer (GC) is the fifth most common cancer and the third most common cause of cancer death worldwide. Plant homeodomain (PHD)-finger domain protein PHF5A has been demonstrated to play a promoting role in a variety of cancers. This study aimed to clarify the role of PHF5A in the progression of GC and its potential mechanism of action.

Methods

Immunohistochemical staining experiments were performed based on tissues from clinical GC patients to reveal PHF5A expression. A series of functional experiments in vitro and in vivo were used to clarify the role of PHF5A in GC.

Results

Clinically, PHF5A was abundantly expressed in GC and existed clinical value indicating poor prognosis. In addition, GC cells with knockdown of PHF5A expression showed slowed proliferation, enhanced sensitivity to apoptosis and inhibition of migration. Mechanically, knockdown of PHF5A led to decreased protein stability of FOS, which was mediated ubiquitination of E3 ubiquitin ligase S-phase kinase-associated protein 2 (SKP2). Moreover, downregulation of FOS attenuated the promotion of PHF5A overexpression on GC cells. Consistently, Pladienolide B (PHF5A inhibitor) treatment reversed the induction of PHF5A overexpression on the malignant phenotypes and tumor formation of GC cells.

Conclusion

Knockdown of PHF5A inhibited the progression of GC through SKP2-mediated ubiquitination of FOS, which may be a promising candidate target with potential therapeutic value.
Associations between self-reported obstetric complications and experience of care: a secondary analysis of survey data from Ghana, Kenya, and India
Authors: Kapula Ntemena , Sacks Emma , Wang Dee T. , Odiase Osamuedeme , Requejo Jennifer , Afulani Patience A. ,   the Revisioning EmONC Quality of Care Workgroup, Benova Lenka , Creanga Andreea , Day Louise Tina , Freedman Lynn , Hill Kathleen , Morgan Allison , Sodzi-Tettey Sodzi , Walker Dilys , Breen Catherine , Monet Jean Pierre , Moran Allisyn , Muzigaba Moise , Maliqi Blerta , Tuncalp Ozge , Hailegebriel Tedbabe
Published: January 2023

Background

Although several indicators have been proposed to measure women’s experience of care in health facilities during the intrapartum period, it is unknown if these indicators perform differently in the context of obstetric emergencies. We examined the relationship between experience of care indicators from the Person-Centered Maternity Care (PCMC) scale and obstetric complications.

Methods

We used data from four cross-sectional surveys conducted in Kenya (rural: N = 873; urban: N = 531), Ghana (N = 531), and India (N = 2018) between August 2016 and October 2017. The pooled sample included 3953 women aged 15–49 years who gave birth within 9 weeks prior to the survey. Experience of care was measured using the PCMC scale. Univariate, bivariate, and multivariable analyses were conducted to examine the associations between the composite and 31 individual PCMC indicators with (1) obstetric complications; (2) severity of complications; and (3) delivery by cesarean section (c-section).

Results

16% (632) of women in the pooled sample reported obstetric complications; and 4% (132) reported having given birth via c-Sect. (10.5% among those with complications). The average standardized PCMC scores (range 0–100) were 63.5 (SD = 14.1) for the full scale, 43.2 (SD = 20.6) for communication and autonomy, 67.8 (SD = 14.1) for supportive care, and 80.1 (SD = 18.2) for dignity and respect sub-scales. Women with complications had higher communication and autonomy scores (45.6 [SD = 20.2]) on average compared to those without complications (42.7 [SD = 20.6]) (p < 0.001), but lower supportive care scores, and about the same scores for dignity and respect and for the overall PCMC. 18 out of 31 experience of care indicators showed statistically significant differences by complications, but the magnitudes of the differences were generally small, and the direction of the associations were inconsistent. In general, women who delivered by c-section reported better experiences.

Conclusions

There is insufficient evidence based on our analysis to suggest that women with obstetric complications report consistently better or worse experiences of care than women without. Women with complications appear to experience better care on some indicators and worse care on others. More studies are needed to understand the relationship between obstetric complications and women’s experience of care and to explore why women who deliver by c-section may report better experience of care.
Theory-based mHealth targeting fathers and mothers to improve exclusive breastfeeding: a quasi-experimental study
Authors: Gebremariam Kidane Tadesse , Mulugeta Afework , Gallegos Danielle
Published: January 2023

Background

Exclusive breastfeeding remains sub-optimal in low-income countries contributing to infant mortality. Mobile health (mHealth) interventions, delivered through personal mobile phones, to improve exclusive breastfeeding have shown promise, but very few include fathers or have been applied in low-income countries. The aim of this study was to assess the effectiveness of a SMS-based breastfeeding intervention targeting fathers and mothers in improving exclusive breastfeeding at three months in a low-income country.

Methods

A quasi-experimental study was carried out with couples in their last trimester of pregnancy, at health centers, Mekelle, Tigray. This study was conducted from September 2018 to March 2019. The SMS-based intervention delivered a total of 16 SMS text messages to two arms: mothers-and-fathers, and mothers-only with the third group acting as the control. The main outcome measure was exclusive breastfeeding at months one, two and three after birth.

Result

There were no significant differences in exclusive breastfeeding at month one between the three, mothers-and-fathers (95.1%), mother-only (90.2%), and control group (85%). At month three 85% of babies were exclusively breastfed in the mothers-and-fathers compared to 60% in the control group (p = 0.01). At month three 80% of babies were exclusively breastfed in the mothers-only compared to 60% in the control group (p = 0.04). In the multivariate analysis, babies born to mothers in the mother-and-fathers group were almost five times more likely to be exclusively breastfeed at three months than babies born to mothers who received standard care [AOR: 4.88, 95% CI (1.35,17.63)].

Conclusion

An mHealth intervention targeting fathers and mothers, and mothers increased the likelihood of babies being exclusively breastfed at three months. The risk of not exclusively breastfeeding in the control group increased over time. A low-cost SMS-based breastfeeding intervention targeting fathers and mothers showed potential to improve exclusive breastfeeding. Such mHealth interventions could be integrated into the antenatal and postnatal follow-up services provided by midwives.

Trial registration

This trial was registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) 12,618,001,481,268.
Intralobar pulmonary sequestration in an adult: a case report
Authors: Sadasivan Nair Prasanth , Merry Christopher , White Alexander
Published: January 2023

Background

Pulmonary sequestration is a rare congenital lung anomaly, presenting mostly in childhood and adolescence.

Case presentation

We report the case of a 26-year-old male patient presenting with pleuritic left sided chest pain and haemoptysis. Computed tomography of the chest showed features of intralobar pulmonary sequestration involving the left lower lobe, with arterial supply arising from the descending thoracic aorta above the diaphragm and normal venous drainage. Video assisted thoracic surgery was planned to perform a left lower lobectomy. Considering the risk of bleeding from the large artery supplying the sequestered segment, a posterolateral thoracotomy incision was made and left lower lobectomy was completed, with successful division of the arterial feeder. The patient was discharged home without complications. Pathologic examination of the specimen grossly revealed partial division of the lobe by two fissures with extensive adhesions into an upper and lower portion with no clear demarcation and a large vessel which enters the lower portion at the posterior inferior aspect, separate from the hilum with a diameter 10 mm. Microscopically, both portions of the lobe showed normally alveolated lung tissue with patchy recent intra-alveolar haemorrhage and evidence of chronic inflammation in the sequestered segment. There was no evidence of malignancy.

Conclusion

This case highlights the rare presentation of pulmonary sequestration in adulthood and the importance of imaging to identify anomalous arterial supply to the sequestered segment in the left lower lobe of the lung. The use of safe surgical techniques to control the anomalous systemic arterial feeding vessel cannot be overemphasized.
Targeting fatty acid synthase modulates sensitivity of hepatocellular carcinoma to sorafenib via ferroptosis
Authors: Li Yan , Yang Wenjuan , Zheng Yuanyuan , Dai Weiqi , Ji Jie , Wu Liwei , Cheng Ziqi , Zhang Jie , Li Jingjing , Xu Xuanfu , Wu Jianye , Yang Mingwei , Feng Jiao , Guo Chuanyong
Published: January 2023

Background

Sorafenib resistance is a key impediment to successful treatment of patients with advanced hepatocellular carcinoma (HCC) and recent studies have reported reversal of drug resistance by targeting ferroptosis. The present study aimed to explore the association of fatty acid synthase (FASN) with sorafenib resistance via regulation of ferroptosis and provide a novel treatment strategy to overcome the sorafenib resistance of HCC patients.

Methods

Intracellular levels of lipid peroxides, glutathione, malondialdehyde, and Fe2+ were measured as indicators of ferroptosis status. Biological information analyses, immunofluorescence assays, western blot assays, and co-immunoprecipitation analyses were conducted to elucidate the functions of FASN in HCC. Both in vitro and in vivo studies were conducted to examine the antitumor effects of the combination of orlistat and sorafenib and CalcuSyn software was used to calculate the combination index.

Results

Solute carrier family 7 member 11 (SLC7A11) was found to play an important role in mediating sorafenib resistance. The up-regulation of FASN antagonize of SLC7A11-mediated ferroptosis and thereby promoted sorafenib resistance. Mechanistically, FASN enhanced sorafenib-induced ferroptosis resistance by binding to hypoxia-inducible factor 1-alpha (HIF1α), promoting HIF1α nuclear translocation, inhibiting ubiquitination and proteasomal degradation of HIF1α, and subsequently enhancing transcription of SLC7A11. Orlistat, an inhibitor of FASN, with sorafenib had significant synergistic antitumor effects and reversed sorafenib resistance both in vitro and in vivo.

Conclusion

Targeting the FASN/HIF1α/SLC7A11 pathway resensitized HCC cells to sorafenib. The combination of orlistat and sorafenib had superior synergistic antitumor effects in sorafenib-resistant HCC cells.
The stromal tumor-infiltrating lymphocytes, cancer stemness, epithelial-mesenchymal transition, and B7-H4 expression in ovarian serous carcinoma
Authors: Hwang Chungsu , Lee Hyun Jung , Na Ju-Young , Kim Ki Hyung , Song Yong Jung , Kim Jee Yeon , Kim Kyungbin , Shin Dong Hoon , Park Joon Young , Kim So Young , Lee Jung Hee , Choi Kyung Un
Published: January 2023

Background

B7-H4 is expressed in various types of cancers and its expression inversely correlates with the degree of tumor-infiltrating lymphocytes (TILs). Studies have shown the relationship between B7-H4, cancer stem cell (CSC) properties, and epithelial-mesenchymal transition (EMT) in various cancers. However, very few studies have investigated the relationship between B7-H4, TILs, cancer stemness, and EMT in epithelial ovarian cancer (EOC). The present study aimed to elucidate whether B7-H4 is involved in immune evasion and examine whether B7-H4 is associated with cancer stemness or EMT in ovarian serous carcinoma, the most common type of EOC. The clinical significance of B7-H4 was also investigated to evaluate its potential as a therapeutic target.

Methods

A total of 145 patients included in this study. The degree of stromal TILs was evaluated using hematoxylin and eosin (H&E)-stained slides. Immunohistochemical analysis of B7-H4, CSC-related biomarkers (CD24, CD44s, CD133, and ALDH1), and EMT-related biomarkers (E-cadherin, N-cadherin, and vimentin) was performed using tissue microarray. qRT-PCR for VTCN1, CD24, CD44, PROM1, ALDH1, CDH1, CDH2, and VIM genes was performed on 38 frozen tissue samples. The mRNA expression levels were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) online analysis tool.

Results

B7-H4 protein expression positively correlated with the degree of stromal TILs. CD24, CD44s, and CD133 expression showed a positive correlation with B7-H4 expression at both the protein and mRNA levels, but ALDH1 correlated only at the protein level. E-cadherin expression was positively correlated with B7-H4 expression at both the protein and mRNA levels. N-cadherin and vimentin expression was inversely related to B7-H4 expression only at the mRNA level. B7-H4 positive patients were associated with higher tumor grade and lower overall survival rate than B7-H4 negative patients, especially in ovarian serous carcinoma with low stromal TILs.

Conclusions

The present study demonstrates that B7-H4 may not be involved in the immune evasion mechanism, but is involved in cancer stemness and mesenchymal-epithelial transition. In addition, B7-H4 may be a therapeutic target for the treatment of ovarian serous carcinoma, especially with low stromal TILs.
Molecular evidence of Borrelia spp. in bats from Córdoba Department, northwest Colombia
Authors: López Yesica , Muñoz-Leal Sebastián , Martínez Caty , Guzmán Camilo , Calderón Alfonso , Martínez Jairo , Galeano Ketty , Muñoz Marina , Ramírez Juan David , Faccini-Martínez Álvaro A. , Mattar Salim
Published: January 2023

Background

The genus Borrelia is composed of two well-defined monophyletic groups, the Borrelia burgdorferi sensu lato complex (Bb) and the relapsing fever (RF) group borreliae. Recently, a third group, associated with reptiles and echidnas, has been described. In general, RF group borreliae use rodents as reservoir hosts; although neotropical bats may also be involved as important hosts, with scarce knowledge regarding this association. The objective of this study was to detect the presence of Borrelia spp. DNA in bats from the department of Córdoba in northwest Colombia.

Methods

During September 2020 and June 2021, 205 bats were captured in six municipalities of Córdoba department, Colombia. Specimens were identified using taxonomic keys and DNA was extracted from spleen samples. A Borrelia-specific real-time PCR was performed for the 16S rRNA gene. Fragments of the 16S rRNA and flaB genes were amplified in the positive samples by conventional PCR. The detected amplicons were sequenced by the Sanger method. Phylogenetic reconstruction was performed in IQ-TREE with maximum likelihood based on the substitution model TPM3+F+I+G4 with bootstrap values deduced from 1000 replicates.

Results

Overall, 10.2% (21/205) of the samples were found positive by qPCR; of these, 81% (17/21) and 66.6% (14/21) amplified 16S rRNA and flaB genes, respectively. qPCR-positive samples were then subjected to conventional nested and semi-nested PCR to amplify 16S rRNA and flaB gene fragments. Nine positive samples for both genes were sequenced, and seven and six sequences were of good quality for the 16S rRNA and flaB genes, respectively. The DNA of Borrelia spp. was detected in the insectivorous and fruit bats Artibeus lituratus, Carollia perspicillata, Glossophaga soricina, Phyllostomus discolor, and Uroderma sp. The 16S rRNA gene sequences showed 97.66–98.47% identity with “Borrelia sp. clone Omi3,” “Borrelia sp. RT1S,” and Borrelia sp. 2374; the closest identities for the flaB gene were 94.02–98.04% with “Borrelia sp. Macaregua.” For the 16S rRNA gene, the phylogenetic analysis showed a grouping with “Candidatus Borrelia ivorensis” and “Ca. Borrelia africana,” and for the flaB gene showed a grouping with Borrelia sp. Macaregua and Borrelia sp. Potiretama. The pathogenic role of the Borrelia detected in this study is unknown.

Conclusions

We describe the first molecular evidence of Borrelia spp. in the department of Córdoba, Colombia, highlighting that several bat species harbor Borrelia spirochetes.

Graphical Abstract
Does the high dietary diversity score predict dietary micronutrients adequacy in children under 5 years old? A systematic review
Authors: Molani-Gol Roghayeh , Kheirouri Sorayya , Alizadeh Mohammad
Published: January 2023

Backgrounds

Undiversified and monotonous diets can lead to deficiency disease, named micronutrient deficiency, more specifically among young children. Dietary diversity (DD) has been known as a valid indicator to assess micronutrient inadequacy of the diet. The aim of this study was to determine “is there an association between high dietary diversity and the micronutrient adequacy, in children under 5 years old?”.

Methods

PubMed, Scopus, ScienceDirect, Web of Sciences, and Google Scholar databases were searched until February 2022, without date restrictions, using relevant keywords. All original articles, written in English, evaluating the relationship between DD and micronutrient adequacy in children under 5 years were eligible for this review.

Results

Totally, 1814 records were found in electronic search databases; after removing duplicated and irrelevant studies according to the title and abstract, the full text of the 35 articles was critically screened, in which 15 cross-sectional studies were included in this review. All of these studies reported that DD of infants and children under 5 years was positively associated with their micronutrient adequacy.

Conclusion

The findings indicate that in infants and children under 5 years, intake of various food groups reveals the adequate intake of micronutrients.
Food hygiene research: a bibliometric comparison in Iranian and international “Environmental Health” journals
Authors: Aghalari Zahra , Dahms Hans-Uwe , Sillanpää Mika
Published: January 2023

Background

Food hygiene is one of the specialized fields of environmental health, and despite the problems associated with foodborne illnesses, there is no evaluation available that would focus on specialized environmental health journals. The purpose of the present survey is a comparison of the status of food hygiene articles published in Iranian and international journals of environmental health.

Methods

This cross-sectional descriptive study was performed on all published articles in five Iranian environmental health journals and three international environmental health journals that are among the top 5% and 10% based on SNIP, emphasizing the issue of food. Our data were collected by searching relevant keywords in the articles published during the years (2008–2021), with emphasis on food hygiene. In the checklist, journal and articles information was collected by year of publication, a number of articles, information on authors' participation status in terms of number, gender, organizational affiliation, country and continents, and research centers according to authors' authorship. Statistical analysis of data was performed using descriptive and inferential statistical indices. VOSviewer software was also used to visualize the data.

Results

In Iranian environmental health journals, out of 2305 articles (7.3%) and out of 6898 articles in international environmental health journals (2.4%) dealt with food hygiene. Food hygiene articles were divided into seven categories, with the largest number of articles on aquatic and agricultural products each with a frequency of 48 articles. Articles related to heavy metals in food were provided by 30.81%. In this study, out of 150 articles, 15 articles were written with the participation of 30 authors from seven continents (Asia, America, and Europe), most of which were from Asia and India. In international environmental health journals, among the main research topics in articles related to food hygiene, the highest number (52.5%) was related to a determination about pollution such as heavy metal concentrations in food.

Conclusions

Articles published in Iranian and international environmental health journals about food hygiene were limited. According to the increasing prevalence of foodborne illnesses, especially in recent decades, and the importance of paying attention to food hygiene, more targeted studies are needed.
Efficacy and risk of mRNA vaccination in patients with autoimmune inflammatory rheumatic diseases
Authors: Kato Yasuhiro , Morita Takayoshi , Kumanogoh Atsushi
Published: January 2023

Coronavirus disease 2019 (COVID-19), which spread worldwide from Wuhan, China, in 2019, appeared for a time to be overcome by the remarkable efficacy of mRNA vaccines; however, new variants of severe acute respiratory syndrome coronavirus 2 have emerged and remain rampant. The involvement of the virus in the emergence of variant strains and the relationship between vaccine efficacy and immunosuppressive drugs have attracted significant attention, particularly with regard to patients with autoimmune inflammatory rheumatic disease (AIRD) who take immunosuppressive drugs. This review outlines the relationship between mRNA vaccines, one of the key strategies against COVID-19, and AIRD and discusses the immune response elicited by mRNA vaccines. Furthermore, the impact of immunosuppressive agents on the mRNA vaccine-induced immune response in patients with AIRD and side effects of the vaccine, such as exacerbation of the underlying disease, is outlined.
Ibrutinib for First-Line Treatment of Chronic Graft-Versus-Host Disease: Results From the Randomized Phase III iNTEGRATE Study
Authors: Miklos David Bernard , Abu Zaid Mohammad , Cooney Julian P. , Albring Jörn C. , Flowers Mary , Skarbnik Alan P. , Yakoub-Agha Ibrahim , Ko Bor-Sheng , Bruno Benedetto , Waller Edmund K. , Yared Jean , Sohn Sang Kyun , Bulabois Claude-Eric , Teshima Takanori , Jacobsohn David , Greinix Hildegard , Mokatrin Ahmad , Lee Yihua , Wahlstrom Justin T. , Styles Lori , Socie Gerard
Published: January 2023

PURPOSE

To present primary and final analyses from the randomized, double-blind, placebo-controlled, phase III iNTEGRATE study, which evaluated the safety and efficacy of ibrutinib with prednisone in previously untreated patients with chronic graft-versus-host disease (cGVHD).

METHODS

Patients (age ≥ 12 years) with newly diagnosed moderate or severe cGVHD, requiring systemic corticosteroid therapy, and with no prior systemic treatment for cGVHD were randomly assigned 1:1 to receive ibrutinib 420 mg once daily plus prednisone, starting at 1 mg/kg once daily or placebo plus prednisone. The primary end point was response rate at 48 weeks according to 2014 National Institutes of Health Consensus Development Project Criteria. Other end points included event-free survival, duration of response, time to withdrawal of immunosuppressants, improvement in Lee cGVHD Symptom Scale score, overall survival (OS), and safety.

RESULTS

Ninety-five and 98 patients enrolled in the ibrutinib-prednisone and placebo-prednisone arms, respectively. At 48 weeks, response rates were 41% (ibrutinib-prednisone) and 37% (placebo-prednisone; P = .54). At 33 months of follow-up, median duration of response was 19 months (ibrutinib-prednisone) and 10 months (placebo-prednisone; P = .10). Median event-free survival was 15 months (ibrutinib-prednisone) and 8 months (placebo-prednisone; hazard ratio, 0.76; 95% CI, 0.54 to 1.1; P = .11). Improvement in overall Lee cGVHD Symptom Scale was 43% (ibrutinib-prednisone) and 31% (placebo-ibrutinib; P = .07). Median OS was not reached in either arm. The 24-month Kaplan-Meier OS estimates were 80% for both arms (hazard ratio, 1.06; 95% CI, 0.59 to 1.90). Grade ≥ 3 serious adverse events occurred in 49% (ibrutinib-prednisone) and 47% (placebo-prednisone) of patients.

CONCLUSION

There was no statistical difference observed in the primary and secondary end points with ibrutinib-prednisone treatment. No new safety signals were observed with ibrutinib treatment in previously untreated patients with cGVHD. The primary end point of iNTEGRATE was not met.
Application of Intraoperative Rapid Molecular Diagnosis in Precision Surgery for Glioma: Mimic the World Health Organization CNS5 Integrated Diagnosis
Authors: Xue Hao , Han Zhe , Li Haiyan , Li Xueen , Jia Deze , Qi Mei , Zhang Hui , Zhang Kailiang , Gong Jie , Wang Hongwei , Feng Zichao , Ni Shilei , Han Bo , Li Gang
Published: January 2023

BACKGROUND:

With the advent of the molecular era, the diagnosis and treatment systems of glioma have also changed. A single histological type cannot be used for prognosis grade. Only by combining molecular diagnosis can precision medicine be realized.

OBJECTIVE:

To develop an automatic integrated gene detection system (AIGS) for intraoperative detection in glioma and to explore its positive role in intraoperative diagnosis and treatment.

METHODS:

We analyzed the isocitrate dehydrogenase 1 (IDH1) mutation status of 105 glioma samples and evaluated the product's potential value for diagnosis; 37 glioma samples were detected intraoperatively to evaluate the feasibility of using the product in an actual situation. A blinding method was used to evaluate the effect of the detection technology on the accuracy of intraoperative histopathological diagnosis by pathologists. We also reviewed the current research status in the field of intraoperative molecular diagnosis.

RESULTS:

Compared with next-generation sequencing, the accuracy of AIGS in detecting IDH1 was 100% for 105 samples and 37 intraoperative samples. The blind diagnostic results were compared between the 2 groups, and the molecular information provided by AIGS increased the intraoperative diagnostic accuracy of glioma by 16.2%. Using the technical advantages of multipoint synchronous detection, we determined the tumor molecular margins for 5 IDH-positive patients and achieved accurate resection at the molecular level.

CONCLUSION:

AIGS can quickly and accurately provide molecular information during surgery. This methodology not only improves the accuracy of intraoperative pathological diagnosis but also provides an important molecular basis for determining tumor margins to facilitate precision surgery.
CCDC66 regulates primary cilium length and signaling via interactions with transition zone and axonemal proteins
Authors: Odabasi Ezgi , Conkar Deniz , Deretic Jovana , Batman Umut , Frikstad Kari-Anne M. , Patzke Sebastian , Firat-Karalar Elif Nur
Published: January 2023

The primary cilium is a microtubule-based organelle that serves as a hub for many signaling pathways. It functions as part of the centrosome or cilium complex, which also contains the basal body and the centriolar satellites. Little is known about the mechanisms by which the microtubule-based ciliary axoneme is assembled with a proper length and structure, particularly in terms of the activity of microtubule-associated proteins (MAPs) and the crosstalk between the different compartments of the centrosome or cilium complex. Here, we analyzed CCDC66, a MAP implicated in cilium biogenesis and ciliopathies. Live-cell imaging revealed that CCDC66 compartmentalizes between centrosomes, centriolar satellites, and the ciliary axoneme and tip during cilium biogenesis. CCDC66 depletion in human cells causes defects in cilium assembly, length and morphology. Notably, CCDC66 interacts with the ciliopathy-linked MAPs CEP104 and CSPP1, and regulates axonemal length and Hedgehog pathway activation. Moreover, CCDC66 is required for the basal body recruitment of transition zone proteins and intraflagellar transport B (IFT-B) machinery. Overall, our results establish CCDC66 as a multifaceted regulator of the primary cilium and provide insight into how ciliary MAPs and subcompartments cooperate to ensure assembly of functional cilia.
Influence of surface free energy of the substrate and flooded water on the attachment performance of stick insects (Phasmatodea) with different adhesive surface microstructures
Authors: Thomas Julian , Gorb Stanislav N. , Büscher Thies H.
Published: January 2023

Stick and leaf insects (Phasmatodea) are exclusively herbivores. As they settle in a broad range of habitats, they need to attach to and walk on a wide variety of plant substrates, which can vary in their surface free energy (SFE). The adhesive microstructures (AMs) on the euplantulae of phasmids are assumed to be adapted to such substrate properties. Moreover, the natural substrates can often be covered with water as a result of high relative humidity or rain. Although considerable experimental research has been carried out on different aspects of stick insect attachment, the adaptations to cope with the influence of flooded water on attachment performance remain unclear. To elucidate the role of AMs in this context, we here measured attachment forces in three species of stick insects with different AMs. The results show that attachment forces of the three species studied were influenced by the SFE and the presence of water: they all showed higher pull-off (vertical) and traction (horizontal) forces on dry surfaces, compared with when the surfaces were covered with a water film. However, the extent to which the surface properties influenced attachment differed depending on the species and its AMs. All three species showed approximately the same attachment performance on dry surfaces with different surface free energy but maintained attachment underwater to different extents.
Silsesquioxane Cage-Fused Siloxane Rings as a Novel Class of Inorganic-Based Host Molecules
Authors: Okamoto Keigo , Imoto Hiroaki , Naka Kensuke
Published: January 2023

Side-opened cage-silsesquioxane, denoted as SO-POSS, was fused with oligo(dimethylsiloxane)s to synthesize inorganic skeleton-based cyclic molecules. The resultant cyclic compounds served as hosts for alkali metal cations (Li+, Na+, K+). Interestingly, ring-transformation occurred in the presence of guest cations depending on the ring size; the SO-POSS-fused cyclic oligo(dimethylsiloxane)s were converted to smaller SO-POSS rings and cyclic oligo(dimethylsiloxane)s. Herein, we report the first study on host-guest chemistry of the cage silsesquioxane-fused siloxane rings.
Photovoltaic Properties of π-Conjugated Polymers Based on Fused Cyclic Imide and Amide Skeletons
Authors: Tsuchii Yuichi , Menda Taiki , Hwang Sunbin , Yasuda Takuma
Published: January 2023

π-Conjugated polymers P(BDT-BTI) and P(BDT-BTA) bearing cyclic imide and amide (lactam) moieties, respectively, were designed and synthesized for application in organic photovoltaics (OPVs). Introducing electron-withdrawing imide and amide moieties lowers the HOMO energy levels of the polymers, resulting in an increase in the open-circuit voltages of OPVs. Complementary photoabsorption over the entire visible range was achieved by combining P(BDT-BTI) and P(BDT-BTA) with a typical non-fullerene acceptor, IT-4F. Unlike P(BDT-BTI), P(BDT-BTA) tends to maintain high crystallinity and retains π–π stacking interactions and face-on orientation in the blend films with IT-4F. Consequently, OPVs based on P(BDT-BTA):IT-4F blends achieved power conversion efficiencies as high as 9.6% without any processing additives or post-treatments.
Prepare for the Unexpected: A New Look at Trauma Triage and Care in Mass Participation Sporting Events
Authors: Sedgley Matt , Hudson Korin , Hulsopple Chad
Published: January 2023

Few sports medicine physicians have extensive experience in managing mass casualty trauma. Yet many, or most, of us find ourselves covering competitions, races, and events in venues where thousands of athletes and spectators gather, and these could quickly become mass casualty events in the setting of an explosion/bombing, active shooter, or similar incident. When this happens, the sports medicine team, already on site, is in a unique position to provide immediate assistance until additional resources arrive. In this article, we will discuss a framework for this initial trauma response to the mass casualty event at a mass participation sporting event.
When Is Air Travel Safe after Mild Traumatic Brain Injury/Sports-Related Concussion?
Authors: Alvarez Bianca E. , McGrew Christopher A. , Bossart Christopher
Published: January 2023

While the literature regarding return to play and recovery protocols from mild traumatic brain injury (mTBI) and sports-related concussions (SRC) is growing, there continues to be a paucity of data regarding when air travel is safe for athletes after sustaining certain brain injuries, such as mTBI and SRC. Although it is known hypoxia can negatively affect severe TBI patients, it is unclear whether mild hypoxia, which may be experienced during commercial air travel, is clinically significant for athletes who have recently sustained mTBI injuries. Further research is required to provide more standardized recommendations on when air travel is safe. With the current available literature, clinicians still need to weigh the evidence, consider how it applies to each individual patient, and engage in shared decision making to ultimately decide what is best for the patient.
Online Sports Medicine Fellowship Education: The Genesis of a National Program and Year-1 Analysis
Authors: Moeller James L. , Zaremski Jason L. , Rao Ashwin , Denq William , Saffel Heather L. , Nye Nathaniel S. , Waterbrook Anna L.
Published: January 2023

The COVID-19 pandemic has created numerous challenges in all walks of life. One such challenge was the strain and subsequent effects on medical education, including the elimination of in-person learning opportunities. Consequently, in March of 2020, a nationwide Sports Medicine fellowship online education series was developed. Presentations were available for live and recorded viewing. Over the course of the 2020–2021 academic year, 38 presentations were offered, covering 45 topics. Live viewership totaled nearly 1600 through the year, while views of recorded lecture reached nearly 34,000. There was no statistical difference in the number of viewers for musculoskeletal versus nonmusculoskeletal topics in either the live (46.50 ± 35.37 vs. 43.38 ± 27.28 viewers, respectively; P = 0.77) or recorded formats (843.60 ± 337.66 vs 876.67 ± 624.70 viewers, respectively; P = 0.85). This article presents the novel approach to sports medicine education by the American Medical Society for Sports Medicine in the 2020–2021 academic year through the genesis the National Online Fellowship Education Program along with analyses of viewership data.
Changes in resting state networks in high school football athletes across a single season
Authors: Ghiles Connor W. , Clark Michael D. , Kuzminski Samuel J. , Fraser Melissa A. , Petrella Jeffrey R. , Guskiewicz Kevin M.
Published: January 2023

Objective:

The aim of this pilot cohort study was to examine changes in the organization of resting-state brain networks in high school football athletes and its relationship to exposure to on-field head impacts over the course of a single season.

Methods:

Seventeen male high school football players underwent functional magnetic resonance imaging and computerized neurocognitive testing (CNS Vital Signs) before the start of contact practices and again after the conclusion of the season. The players were equipped with helmet accelerometer systems (Head Impact Telemetry System) to record head impacts in practices and games. Graph theory analysis was applied to study intranetwork local efficiency and strength of connectivity within six anatomically defined brain networks.

Results:

We observed a significant decrease in the local efficiency (−24.9 ± 51.4%, r = 0.7, p < 0.01) and strength (−14.5 ± 26.8%, r = 0.5, p < 0.01) of functional connectivity within the frontal lobe resting-state network and strength within the parietal lobe resting-state network (−7.5 ± 17.3%, r = 0.1, p < 0.01), as well as a concomitant increase in the local efficiency (+55.0 +/- 59.8%, r = 0.5, p < 0.01) and strength (+47.4 +/- 47.3%, r = 0.5, p < 0.01) within the mediotemporal networks. These alterations in network organization were associated with changes in performance on verbal memory (p < 0.05) and executive function (p < 0.05). We did not observe a significant relationship between the frequency or cumulative magnitude of impacts sustained during the season and neurocognitive or imaging outcomes (p > 0.05).

Conclusion:

Our findings suggest the efficiency and strength of resting-state networks are altered across a season of high school football, but the association of exposure levels to subconcussive impacts is unclear.

Advances in knowledge:

The efficiency of resting-state networks is dynamic in high school football athletes; such changes may be related to impacts sustained during the season, though further study is needed.
Differences in MRI findings of superficial spindle cell lipoma and atypical lipomatous tumor/well-differentiated liposarcoma
Authors: Kawaguchi Masaya , Kato Hiroki , Kobayashi Kazuhiro , Miyazaki Tatsuhiko , Nagano Akihito , Noda Yoshifumi , Hyodo Fuminori , Matsuo Masayuki
Published: January 2023

Objective:

This study aimed to evaluate the efficacy of using MRI findings to differentiate superficial spindle cell lipomas (SCLs) from atypical lipomatous tumor/well-differentiated liposarcomas (ALT/WDLs).

Methods:

This study included 12 patients with histopathologically proven superficial SCLs and 11 with ALT/WDLs. MRI findings for both pathologies were retrospectively reviewed and compared between the two pathologies.

Results:

The neck, upper back, and shoulder regions were more frequent locations of SCLs than of ALT/WDLs (100% vs 55%, p < 0.05), whereas no significant differences were observed in age and sex. The median maximum diameter of the lesion was smaller in SCLs than in ALT/WDLs (44 mm [interquartile range (IQR): 35–63] vs 102 mm [IQR: 86–119], p < 0.05). On T 1 weighted images, non-fatty area was more frequently observed in SCLs than in ALT/WDLs (73% vs 25%, p < 0.05), and the median rate of non-fatty area was larger in SCLs than in ALT/WDLs (7.5% [IQR: 1.0–53] vs 0% [IQR: 0–0.2], p < 0.05). On fat-suppressed T 2 weighted images, a solid hyperintense area was more frequently observed in SCLs than in ALT/WDLs (83% vs 27%, p < 0.05).

Conclusion:

The maximum diameter, non-fatty area on T 1 weighted images, and solid hyperintense area on fat-suppressed T 2 weighted images were useful imaging features for differentiating superficial SCLs from ALT/WDLs.

Advances in knowledge:

In superficial lipomatous tumors, small tumor size and non-fatty solid area were valuable findings for diagnosing SCLs.
Stroke prevention – review of the latest reports
Authors: Kasperski Radosław , Piekarska Małgorzata , Pacek Katarzyna , Pikulicka Agata , Szulc Izabela , Jedlina Klaudia , Swacha Weronika , Świercz Kamila
Published: January 2023

Introduction and purpose: According to WHO 15 million people suffer from stroke, one-third of which dies and  the other one-third is permanently disabled. For this reason, this condition is a very important medical and social problem. It is one of the leading causes of death, after cardiovascular diseases and cancer. It is also one of the most common causes of disability in the adult population. The economic aspects are related not only to the costs of hospital treatment, but above all to rehabilitation and chronic treatment. The aim of this article is to present the most important stroke risk factors and, based on them, to describe recommendations for effective stroke prevention.

A brief description of the state of knowledge: In recent years, numerous studies have been conducted on the relationship between various factors and the risk of stroke. It turned out that many stroke risk factors are modifiable and by using various methods we are able to significantly reduce the risk of its occurrence. The most important risk factor is the patient's hypertension. Others are cardiovascular diseases such as atrial fibrillation; diabetes, obesity, low level of physical activity, improper diet, consumption of alcohol and tobacco products.

Summary: Through education and promotion of a healthy lifestyle in society (high physical activity, healthy diet, lack of addictions, taking care of mental health and avoiding excessive stress), as well as regular blood pressure and glucose control and effective treatment of conditions leading to stroke, the incidence of stroke among people can actually be reduced. This issue still requires further research and constant expansion of our knowledge.
Does a One-Size-Fits-All Minimum Wage Cause Financial Stress for Small Businesses?
Authors: Chava Sudheer , Oettl Alexander , Singh Manpreet
Published: January 2023

Using intertemporal variation in the bounding of a state’s minimum wage by the federal rate and business credit-score data for 15.2 million establishments, we find that the increase in labor costs caused by a higher federal minimum wage leads to lower business credit scores and worsens the financial health of small businesses in the affected states. In particular, small, young, labor-intensive, and minimum-wage-sensitive establishments located in affected states and those located in competitive and low-income areas experience higher financial stress. Increases in the minimum wage are associated with employment reductions and a higher exit rate for small businesses. Our results document some potential costs of a one-size-fits-all nationwide minimum wage for some small businesses.

This paper was accepted by Gustavo Manso, finance.

Funding: This work was supported by the Ewing Marion Kauffman Foundation Junior Faculty Fellowship.

Supplemental Material: The data and internet appendix are available at https://doi.org/10.1287/mnsc.2022.4620 .