bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-lasting postoperative analgesia with local anesthetic-loaded hydrogels prevent tumor recurrence via enhancing CD8+T cell infiltration
Authors: Zhao Mingxu , Zhu Shasha , Zhang Ding , Zhou Chang , Yang Zhilai , Wang Chunhui , Liu Xuesheng , Zhang Jiqian
Published: February 2023

Postoperative pain (POP) can promote tumor recurrence and reduce the cancer patient's quality of life. However, POP management has always been separated from tumor treatment in clinical practice, and traditional postoperative analgesia using opioids is still unsatisfactory for patients, which is not conducive to tumor treatment. Here, ropivacaine, a popular amide-type LA, was introduced into a Pluronic F127 hydrogel. Postoperative analgesia with ropivacaine-loaded hydrogels reduced the incidence of high-dose ropivacaine-induced convulsions and prolonged pain relief for more than 16 h. More interestingly, ropivacaine-loaded hydrogel was found to upregulate major histocompatibility complex class I (MHC-I) in tumor cells by impairing autophagy. Therefore, a hydrogel co-dopped with ropivacaine and TLR7 agonist imiquimod (PFRM) was rationally synthesized. After postoperative analgesia with PFRM, imiquimod primes tumor-specific CD8+T cells through promoting DCs maturation, and ropivacaine facilitates tumor cells recognition by primed CD8+T cells through upregulating MHC-I. Consequently, postoperative analgesia with PFRM maximumly increases CD8+T cells infiltration into residual tumor tissue and prevents tumor recurrence. Overall, this study for the first time provides an LA-based approach for simultaneous long-lasting postoperative analgesia and prevention of tumor recurrence.
The members of the miR-148/152 family inhibit cancer stem cell-like properties in gastric cancer via negative regulation of ITGA5
Authors: Li Xiaoying , Li Lin , Wu Jiangying
Published: February 2023

Background

The role of microRNA (miRNA) in modulating the function of cancer stem cells through diverse signaling pathway has been evidenced. We here identified a role of microRNA (miRNA) family, specifically miR-148/152, in gastric cancer and delineated its functional effects on gastric cancer stem cells.

Methods

Bioinformatics analysis was conducted to analyze expression of integrin α5 (ITGA5) which was verified through expression determination in clinical tissue samples. Next, the upstream regulatory factors of ITGA5 were determined. CD44+EpCAM (high) cells sorted from AGS cells subjected to gain-of-function experiments, followed by evaluation of their capacity of colony formation, generation of tumorosphere, cell migration and viability in vitro and xenograft tumor formation in vivo.

Results

ITGA5 was elevated in gastric cancer tissues and confirmed as a target gene of the miR-148/152 family members. The miR-148/152 family members were downregulated in gastric cancer tissues and cells. Decreased expression of miR-148/152 family members was also detected in gastric cancer stem cells. However, the raised expression led to reduced colony formation, tumorosphere, cell migration, cell viability, and drug resistance of CD44+EpCAM (high) AGS cells in vitro, and tumorigenesis in vitro. ITGA5 overexpression reversed the effect of the miR-148/152 family members.

Conclusions

This study demonstrates that the miR-148/152 family members may prevent gastric cancer stem cell-like properties by targeting ITGA5, which can serve as an appealing target for gastric cancer treatment.
The genetic basis of multiple system atrophy
Authors: Tseng Fan Shuen , Foo Joel Qi Xuan , Mai Aaron Shengting , Tan Eng-King
Published: February 2023

Multiple system atrophy (MSA) is a heterogenous, uniformly fatal neurodegenerative ɑ-synucleinopathy. Patients present with varying degrees of dysautonomia, parkinsonism, cerebellar dysfunction, and corticospinal degeneration. The underlying pathophysiology is postulated to arise from aberrant ɑ-synuclein deposition, mitochondrial dysfunction, oxidative stress and neuroinflammation. Although MSA is regarded as a primarily sporadic disease, there is a possible genetic component that is poorly understood. This review summarizes current literature on genetic risk factors and potential pathogenic genes and loci linked to both sporadic and familial MSA, and underlines the biological mechanisms that support the role of genetics in MSA. We discuss a broad range of genes that have been associated with MSA including genes related to Parkinson’s disease (PD), oxidative stress, inflammation, and tandem gene repeat expansions, among several others. Furthermore, we highlight various genetic polymorphisms that modulate MSA risk, including complex gene–gene and gene-environment interactions, which influence the disease phenotype and have clinical significance in both presentation and prognosis. Deciphering the exact mechanism of how MSA can result from genetic aberrations in both experimental and clinical models will facilitate the identification of novel pathophysiologic clues, and pave the way for translational research into the development of disease-modifying therapeutic targets.
Association between oxidative stress, mitochondrial function of peripheral blood mononuclear cells and gastrointestinal cancers
Authors: Liu Weili , Gao Yuan , Li Hua , Wang Xinxing , Jin Min , Shen Zhiqiang , Yang Dong , Zhang Xuelian , Wei Zilin , Chen Zhaoli , Li Junwen
Published: February 2023

Background

The incidence and mortality rate of gastrointestinal cancers are high worldwide. Increasing studies have illustrated that the occurrence, progression, metastasis and prognosis of cancers are intimately linked to the immune system. Mitochondria, as the main source of cellular energy, play an important role in maintaining the physiological function of immune cells. However, the relationship between mitochondrial function of immune cells and tumorigenesis has not yet been systematically investigated.

Methods

A total of 150 cases, including 60 healthy donors and 90 primary gastrointestinal cancer patients without anti-tumor treatments (30 with gastric cancer, 30 with liver cancer and 30 with colorectal cancer) were involved in our study. The oxidant/antioxidant and cytokine levels in plasma, the ROS level, mitochondrial function and apoptosis ratio of peripheral blood mononuclear cells (PBMCs) were evaluated.

Results

The imbalance between oxidant and antioxidant in plasma was discovered in the primary gastrointestinal cancer patients. The levels of cell reactive oxygen species (ROS) and mitochondrial ROS in PBMCs of primary gastrointestinal cancers were significantly increased compared with that in healthy donors. Meanwhile, the ATP content, the mtDNA copy number and the mitochondrial membrane potential (MMP) in PBMCs of patients with primary gastrointestinal cancers were lower than those in control group. The decreased MMP also occurred in immune cells of gastrointestinal cancers, including T cell, B cell, NK cell and monocyte. Furthermore, the PBMCs apoptosis ratio of primary gastrointestinal cancer patients was significantly higher than that of control group. Importantly, an increase of IL-2 and IL-6 and a decrease of IgG in plasma were found in the patients with primary gastrointestinal cancers. These changes of mitochondrial function in immune cells were consistent among primary gastrointestinal cancers without anti-tumor treatments, such as liver cancer, gastric cancer and colorectal cancer.

Conclusion

Our study demonstrated that the imbalance of oxidation/antioxidation in primary gastrointestinal cancer patients without anti-tumor treatments results in excessive ROS. The oxidative stress was associated to the mitochondrial dysfunction, the apoptosis of immune cells and eventually the abnormal immune function in primary gastrointestinal cancers. The application of immune cell mitochondrial dysfunction into clinical evaluation is anticipated.
Cellular senescence in the response of HR+ breast cancer to radiotherapy and CDK4/6 inhibitors
Authors: Klapp Vanessa , Buqué Aitziber , Bloy Norma , Sato Ai , Yamazaki Takahiro , Zhou Xi Kathy , Formenti Silvia C. , Galluzzi Lorenzo , Petroni Giulia
Published: February 2023

Background

Preclinical evidence from us and others demonstrates that the anticancer effects of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors can be enhanced with focal radiation therapy (RT), but only when RT is delivered prior to (rather than after) CDK4/6 inhibition. Depending on tumor model, cellular senescence (an irreversible proliferative arrest that is associated with the secretion of numerous bioactive factors) has been attributed beneficial or detrimental effects on response to treatment. As both RT and CDK4/6 inhibitors elicit cellular senescence, we hypothesized that a differential accumulation of senescent cells in the tumor microenvironment could explain such an observation, i.e., the inferiority of CDK4/6 inhibition with palbociclib (P) followed by RT (P→RT) as compared to RT followed by palbociclib (RT→P).

Methods

The impact of cellular senescence on the interaction between RT and P was assessed by harnessing female INK-ATTAC mice, which express a dimerizable form of caspase 8 (CASP8) under the promoter of cyclin dependent kinase inhibitor 2A (Cdkn2a, coding for p16Ink4), as host for endogenous mammary tumors induced by the subcutaneous implantation of medroxyprogesterone acetate (MPA, M) pellets combined with the subsequent oral administration of 7,12-dimethylbenz[a]anthracene (DMBA, D). This endogenous mouse model of HR+ mammary carcinogenesis recapitulates key immunobiological aspects of human HR+ breast cancer. Mice bearing M/D-driven tumors were allocated to RT, P or their combination in the optional presence of the CASP8 dimerizer AP20187, and monitored for tumor growth, progression-free survival and overall survival. In parallel, induction of senescence in vitro, in cultured human mammary hormone receptor (HR)+ adenocarcinoma MCF7 cells, triple negative breast carcinoma MDA-MB-231 cells and mouse HR+ mammary carcinoma TS/A cells treated with RT, P or their combination, was determined by colorimetric assessment of senescence-associated β-galactosidase activity after 3 or 7 days of treatment.

Results

In vivo depletion of p16Ink4-expressing (senescent) cells ameliorated the efficacy of P→RT (but not that of RT→P) in the M/D-driven model of HR+ mammary carcinogenesis. Accordingly, P→RT induced higher levels of cellular senescence than R→TP in cultured human and mouse breast cancer cell lines.

Conclusions

Pending validation in other experimental systems, these findings suggest that a program of cellular senescence in malignant cells may explain (at least partially) the inferiority of P→RT versus RT→P in preclinical models of HR+ breast cancer.
Pulmonary sclerosing pneumocytoma containing spindle cells with sarcomatoid features: a case report with literature review
Authors: Liang Jing , Du Qiang , Ye Xiaoxing , Huang Wenting
Published: February 2023

Background

Pulmonary sclerosing pneumocytoma (PSP) is an uncommon benign neoplasm originated from pneumocyte and PSP with malignant transformation is extremely rare.

Case presentation

We report a case of PSP of a 65-year-old male patient presented as a lobulated mass in the upper lobe of the left lung, in which part of the stromal round cells transformed to spindle cells with sarcomatoid features and showed no specific differentiation. The patient underwent partial lobectomy without further treatment. No recurrence and metastasis was found after eight month’s follow up.

Conclusions

To our knowledge, this is the first case of PSP with sarcomatoid malignant transformation devoid of differentiation. Our case adds the evidence in that a subset of PSP bear malignant potential and more studies are needed in order to determine the treatment and prognosis to such patients.
Combining aortic arch dissection stent implantation and root surgery for aortic dissection type A
Authors: Immohr Moritz Benjamin , Mehdiani Arash , Bauer Sebastian Johannes , Ise Hayato , Sugimura Yukiharu , Lichtenberg Artur , Akhyari Payam
Published: February 2023

Background

Acute aortic dissection type A (AADA) is associated with high perioperative morbidity and mortality. A novel non-covered hybrid prosthesis (AMDS, CryoLife, Kennesaw, USA) can be easily implanted to stabilize the true lumen. However, the role of AMDS for patients requiring additional aortic root surgery has not been described.

Methods

Between 2010 and 2020 a total of n = 370 patients underwent surgery for AADA in our department. Of those, n = 120 underwent treatment for aortic root in addition to proximal arch replacement without resection of the aorta beyond the innominate artery (Control, n = 111) and were compared to patients who received additional AMDS implantation (AMDS, n = 9).

Results

Aortic valve repair was performed in 48.6% (Control) and in 55.6% of AMDS patients. Cardiopulmonary bypass (Control: 248 ± 76 min, AMDS: 313 ± 53 min, P < 0.01) time as well as circulatory arrest time of the lower body (Control: 30 ± 15 min, AMDS: 52 ± 12 min, P < 0.01) was prolonged in the AMDS group. Nevertheless, postoperative in-hospital morbidity such as dialysis (Control: 22.4%, AMDS: 11.1%, P = 0.68) and stroke (Control: 17.0%, AMDS: 22.2%, P = 0.65) were comparable. In-hospital death (Control: 21.8%, AMDS: 11.1%, P = 0.68) and the compound end-point MACCE (Control: 38.7%, AMDS: 44.4%, P = 0.74) did also not differ.

Conclusions

Addressing the arch by implantation of AMDS prolongs cardiopulmonary bypass and circulatory arrest time, however without relevant impairments of short-term outcome. Combining root surgery with replacement of the proximal aortic arch and AMDS implantation seems feasible and safe as it did not impair the early postoperative outcome.
Quality of recovery after day care surgery with app-controlled remote monitoring: study protocol for a randomized controlled trial
Authors: Thiel B. , Godfried M. B. , van Emst M. E. , Vernooij L. M. , van Vliet L. M. , Rumke E. , van Dongen R. T. M. , Gerrits W. , Koopman J. S. H. A. , Kalkman C. J.
Published: February 2023

Background

The majority of surgical interventions are performed in day care and patients are discharged after the first critical postoperative period. At home, patients have limited options to contact healthcare providers in the hospital in case of severe pain and nausea. A smartphone application for patients to self-record pain and nausea when at home after day care surgery might improve patient’s recovery. Currently patient experiences with smartphone applications are promising; however, we do not know whether remote monitoring with such an application also improves the patient’s recovery. This study aims to evaluate the experienced quality of recovery after day care surgery between patients provided with the smartphone application for remote monitoring and patients receiving standard care without remote monitoring.

Methods

This non-blinded randomized controlled trial with mixed methods design will include 310 adult patients scheduled for day care surgery.

The intervention group receives the smartphone application with text message function for remote monitoring that enables patients to record pain and nausea. An anaesthesia professional trained in empathetic communication, who will contact the patient in case of severe pain or nausea, performs daily monitoring. The control group receives standard care, with post-discharge verbal and paper instructions.

The main study endpoint is the difference in perceived quality of recovery, measured with the QoR-15 questionnaire on the 7th day after day care surgery. Secondary endpoints are the overall score on the Quality of Recovery-15 at day 1, 4 and 7-post discharge, the perceived quality of hospital aftercare and experienced psychological effects of remote monitoring during postoperative recovery from day care surgery.

Discussion

This study will investigate if facilitating patients and healthcare professionals with a tool for accessible and empathetic communication might lead to an improved quality of the postoperative recovery period.

Trial registration

The ‘Quality of recovery after day care surgery with app-controlled remote monitoring: a randomized controlled trial’ is approved and registered on 23 February 2022 by Research Ethics Committees United with registration number R21.076/NL78144.100.21. The protocol NL78144.100.21, ‘Quality of recovery after day care surgery with app-controlled remote monitoring: a randomized controlled trial’, is registered at the ClinicalTrials.gov public website (registration date 16 February 2022; NCT05244772)
Interferon and interferon-induced cytokines as markers of impending clinical progression in ANA+ individuals without a systemic autoimmune rheumatic disease diagnosis
Authors: Kim Sonya T. , Muñoz-Grajales Carolina , Dunn Shannon E. , Schneider Raphael , Johnson Sindhu R. , Touma Zahi , Ahmad Zareen , Bonilla Dennisse , Atenafu Eshetu G. , Hiraki Linda T. , Bookman Arthur , Wither Joan
Published: February 2023

Background

Elevated levels of interferons (IFNs) are a characteristic feature of systemic autoimmune rheumatic diseases (SARDs) and may be useful in predicting impending symptomatic progression in anti-nuclear antibody-positive (ANA+) individuals lacking a SARD diagnosis. Typically, these are measured by their effect on gene expression in the blood, which has limited their utility in clinical settings. Here, we assessed whether the measurement of serum IFN-α or selected IFN-induced cytokines accurately mirrors IFN-induced gene expression in ANA+ individuals and investigated their utility as biomarkers of clinical progression.

Methods

A total of 280 subjects were studied, including 50 ANA− healthy controls, 160 ANA+ individuals without a SARD diagnosis (96 asymptomatic, 64 with undifferentiated connective tissue disease), and 70 SARD patients. IFN-induced gene expression was measured by nanoString and cytokine levels by ELISA or Simoa. ANA+ individuals lacking a SARD diagnosis who had the new onset of SARD criteria over the subsequent 2 years were defined as progressors.

Results

Measurement of IFN-α levels by high-sensitivity ELISA or Simoa correlated much better with IFN-induced gene expression than measurement of CXCL-10 or Galectin-9 levels. Despite this, high CXCL-10 and Galectin-9 levels were better predictors of subsequent progression in ANA+ individuals than measures of IFN-α or IFN-induced gene expression with the optimal combination of predictive cytokines (CXCL-10 and IFN-α as measured by ELISA), resulting in a specificity and positive predictive value of 100%.

Conclusion

Easily performed ELISA assays for CXCL-10 and IFN-α can be used to predict ANA+ individuals at high risk of imminent symptomatic progression.
Accuracy of linear-probe ultrasonography in diagnosis of infraorbital rim fractures
Authors: Pruksapong Chatchai , Wongprakob Nuttadon , Panphichet Minth
Published: February 2023

Background

Maxillofacial fractures are a common cause of visits to emergency department, accounting for more than 400,000 annual visits in the United States. Gold standard diagnostic tool is conventional computerized tomography (CT) or 3DCT reconstruction. However, the disadvantages of CT are radiation exposure, unavailable in some hospital and expensiveness. Whereas the bony structures overlap is a problem in diagnostic when using plain film X-ray. The objective of this study is to show the accuracy of a linear-probe ultrasound compared to computed tomography and plain film X-ray in diagnosis of infraorbital rim fracture.

Methods

Patients clinically suspected of an inferior orbital rim fracture underwent linear-probe ultrasonographic investigation, plain film X-ray and CT. CT was used as gold standard in this diagnostic study. A radiologist and senior resident of plastic surgery were the examiner and interobserver for comparison.

Result

A total of 34 patients with suspected infraorbital rim fractures were investigated. Sensitivity of the linear-probe ultrasonography versus CT in the detection of infraorbital rim fracture was 92.9% (95% CI 66.1–99.8), specificity was 90.0% (95% CI 68.3–98.8), positive predictive value was 86.7% (95% CI 59.5–98.3), negative predictive value was 94.7% ( 95% CI 74.0–99.9), accuracy 91%.

Conclusion

Linear probe ultrasonography is a good diagnostic tool and has better reliability than the plain film X-ray and can be used as alternative to CT in inferior orbital rim fracture.
Clinical outcomes of a large-scale, partnership-based regional food prescription program: results of a quasi-experimental study
Authors: Ranjit Nalini , Aiyer Jennifer N. , Toups Jack D. , Liew Esther , Way Kenia , Brown Henry Shelton , McWhorter John Wesley , Sharma Shreela V.
Published: February 2023

Background

Food prescription programs are gaining interest from funders, policy makers, and healthcare payers as a way to provide value-based care. A small body of research suggests that such programs effectively impact health outcomes; however, the quality of existing studies is variable, and most studies use small samples. This study attempts to address these gaps by utilizing a quasi-experimental design with non-equivalent controls, to evaluate clinical outcomes among participants enrolled in a food prescription program implemented at scale.

Methods

We completed a secondary analysis of participant enrollment and utilization data collected between May 2018 and March 2021, by the Houston Food Bank as part of its multi-institution food prescription program. Enrollment data was obtained from 16 health care partners and redemption data from across 40 food pantries in Houston, Texas. Our objective was to assess if program participation impacted multiple cardio-metabolic markers. Exposure was defined as any visit to a food pantry after receipt of prescription. Linear and logistic regression models were used to estimate change in outcomes by exposure status and number of food pantry visits.

Results

Exposed patients experienced a −0.28% (p = 0.007) greater change in HbA1c than unexposed patients, over six months. Differences across exposure categories were seen with systolic blood pressure (−3.2, p < 0.001) and diastolic blood pressure (−2.5, p = 0.028), over four months. The odds of any decline in HbA1c (OR = 1.06 per visit, p < 0.001) and clinically meaningful decline in HbA1c (OR = 1.04 per visit, p = 0.007) showed a linear association with visit frequency.

Conclusions

Our study of a large food prescription program involving multiple health care and food pantry sites provides robust evidence of a modest decline in HbA1c levels among participants. These results confirm that food prescription programs can continue to be effective at scale, and portend well for institutionalization of such programs.
Neural biomarker diagnosis and prediction to mild cognitive impairment and Alzheimer’s disease using EEG technology
Authors: Jiao Bin , Li Rihui , Zhou Hui , Qing Kunqiang , Liu Hui , Pan Hefu , Lei Yanqin , Fu Wenjin , Wang Xiaoan , Xiao Xuewen , Liu Xixi , Yang Qijie , Liao Xinxin , Zhou Yafang , Fang Liangjuan , Dong Yanbin , Yang Yuanhao , Jiang Haiyan , Huang Sha , Shen Lu
Published: February 2023

Background

Electroencephalogram (EEG) has emerged as a non-invasive tool to detect the aberrant neuronal activity related to different stages of Alzheimer’s disease (AD). However, the effectiveness of EEG in the precise diagnosis and assessment of AD and its preclinical stage, amnestic mild cognitive impairment (MCI), has yet to be fully elucidated. In this study, we aimed to identify key EEG biomarkers that are effective in distinguishing patients at the early stage of AD and monitoring the progression of AD.

Methods

A total of 890 participants, including 189 patients with MCI, 330 patients with AD, 125 patients with other dementias (frontotemporal dementia, dementia with Lewy bodies, and vascular cognitive impairment), and 246 healthy controls (HC) were enrolled. Biomarkers were extracted from resting-state EEG recordings for a three-level classification of HC, MCI, and AD. The optimal EEG biomarkers were then identified based on the classification performance. Random forest regression was used to train a series of models by combining participants’ EEG biomarkers, demographic information (i.e., sex, age), CSF biomarkers, and APOE phenotype for assessing the disease progression and individual’s cognitive function.

Results

The identified EEG biomarkers achieved over 70% accuracy in the three-level classification of HC, MCI, and AD. Among all six groups, the most prominent effects of AD-linked neurodegeneration on EEG metrics were localized at parieto-occipital regions. In the cross-validation predictive analyses, the optimal EEG features were more effective than the CSF + APOE biomarkers in predicting the age of onset and disease course, whereas the combination of EEG + CSF + APOE measures achieved the best performance for all targets of prediction.

Conclusions

Our study indicates that EEG can be used as a useful screening tool for the diagnosis and disease progression evaluation of MCI and AD.
The role of non-additive gene action on gene expression variation in plant domestication
Authors: Díaz-Valenzuela Erik , Hernández-Ríos Daniel , Cibrián-Jaramillo Angélica
Published: February 2023

Background

Plant domestication is a remarkable example of rapid phenotypic transformation of polygenic traits, such as organ size. Evidence from a handful of study cases suggests this transformation is due to gene regulatory changes that result in non-additive phenotypes. Employing data from published genetic crosses, we estimated the role of non-additive gene action in the modulation of transcriptional landscapes in three domesticated plants: maize, sunflower, and chili pepper. Using A. thaliana, we assessed the correlation between gene regulatory network (GRN) connectivity properties, transcript abundance variation, and gene action. Finally, we investigated the propagation of non-additive gene action in GRNs.

Results

We compared crosses between domesticated plants and their wild relatives to a set of control crosses that included a pair of subspecies evolving under natural selection and a set of inbred lines evolving under domestication. We found abundance differences on a higher portion of transcripts in crosses between domesticated-wild plants relative to the control crosses. These transcripts showed non-additive gene action more often in crosses of domesticated-wild plants than in our control crosses. This pattern was strong for genes associated with cell cycle and cell fate determination, which control organ size. We found weak but significant negative correlations between the number of targets of trans-acting genes (Out-degree) and both the magnitude of transcript abundance difference a well as the absolute degree of dominance. Likewise, we found that the number of regulators that control a gene’s expression (In-degree) is weakly but negatively correlated with the magnitude of transcript abundance differences. We observed that dominant-recessive gene action is highly propagable through GRNs. Finally, we found that transgressive gene action is driven by trans-acting regulators showing additive gene action.

Conclusions

Our study highlights the role of non-additive gene action on modulating domestication-related traits, such as organ size via regulatory divergence. We propose that GRNs are shaped by regulatory changes at genes with modest connectivity, which reduces the effects of antagonistic pleiotropy. Finally, we provide empirical evidence of the propagation of non-additive gene action in GRNs, which suggests a transcriptional epistatic model for the control of polygenic traits, such as organ size.
Parents' knowledge and predictions about the age of menarche: experimental evidence from Honduras
Authors: Accerenzi Michela , Brañas-Garza Pablo , Jorrat Diego
Published: February 2023

Background

Access to accurate, timely and age-appropriate information about menarche is an essential part of menstrual health. Reliable evidence shows that girls primarily obtain information from their mothers and/or other female family members, therefore, it is important to determine parents’ knowledge and their predictions about other parents’ knowledge of the age of menarche.

Methods

To this end, we performed a pre-registered study with data collected from 360 households in Santa Rosa de Copán, Honduras. We implemented a novel procedure to avoid social desirability bias whereby participants answered two separated questions: i) their knowledge about the age of menarche (self-report) and ii) to predict or guess the modal response of the other participants regarding the same question (modal guess). Participants were paid according to accuracy. Both questions appeared randomly in the survey.

Results

Recent studies indicate the age of menarche at 12 years old and 56.11% of the sample gave the same response while 62.78% hit the modal value. We estimated the impact of different sociodemographic variables and found only marginal differences. Interestingly, people with formal education and women tend to respond with lower predictions.

Conclusion

Parents’ knowledge about the age of menarche is high in the study area. The study also found that there was no social desirability bias.
Reliability and validity of a Global Physical Activity Questionnaire adapted for use among pregnant women in Nepal
Authors: Algallai Noha , Martin Kelly , Shah Krupali , Shrestha Kusum , Daneault Jean-Francois , Shrestha Archana , Shrestha Abha , Rawal Shristi
Published: February 2023

Background

Physical activity (PA) plays an important role in optimizing health outcomes throughout pregnancy. In many low-income countries, including Nepal, data on the associations between PA and pregnancy outcomes are scarce, likely due to the lack of validated questionnaires for assessing PA in this population. Here we aimed to evaluate the reliability and validity of an adapted version of Global Physical Activity Questionnaire (GPAQ) among a sample of pregnant women in Nepal.

Methods

A cohort of pregnant women (N=101; age 25.9±4.1 years) was recruited from a tertiary, peri-urban hospital in Nepal. An adapted Nepali version of GPAQ was administered to gather information about sedentary behavior (SB) as well as moderate and vigorous PA across work/domestic tasks, travel (walking/bicycling), and recreational activities, and was administered twice and a month apart in both the 2nd and 3rd trimesters. Responses on GPAQ were used to determine SB (min/day) and total moderate to vigorous PA (MVPA; min/week) across all domains. GPAQ was validated against PA data collected by a triaxial accelerometer (Axivity AX3; UK) worn by a subset of the subjects (n=21) for seven consecutive days in the 2nd trimester. Intra-class correlation coefficients (ICC) and Spearman’s rho were used to assess the reliability and validity of GPAQ.

Results

Almost all of the PA in the sample was attributed to moderate activity during work/domestic tasks or travel. On average, total MVPA was higher by 50 minutes/week in the 2nd trimester as compared to the 3rd trimester. Based on the World Health Organization (WHO) guidelines, almost all of the participants were classified as having a low or moderate level of PA. PA scores for all domains showed moderate to good reliability across both the 2nd and 3rd trimesters, with ICCs ranging from 0.45 (95%CI: (0.17, 0.64)) for travel PA at 2nd trimester to 0.69 (95%CI: (0.51, 0.80)) for travel PA at 3rd trimester. Reliability for total MVPA was higher in the 3rd trimester compared to 2nd trimester [ICCs 0.62 (0.40, 0.75) vs. 0.55 (0.32, 0.70)], whereas the opposite was true for SB [ICCs 0.48 (0.19, 0.67) vs. 0.64 (0.46, 0.76)]. There was moderate agreement between the GPAQ and accelerometer for total MVPA (rho = 0.42; p value <0.05) while the agreement between the two was poor for SB (rho= 0.28; p value >0.05).

Conclusions

The modified GPAQ appears to be a reliable and valid tool for assessing moderate PA, but not SB, among pregnant women in Nepal.
Risk of childhood trauma exposure and severity of bipolar disorder in Colombia
Authors: Guillen-Burgos Hernán , Moreno-Lopez Sergio , Acevedo-Vergara Kaleb , Pérez-Florez Manuel , Pachón-Garcia Catherine , Gálvez-Flórez Juan Francisco
Published: February 2023

Background

Bipolar disorder (BD) is higher in developing countries. Childhood trauma exposure is a common environmental risk factor in Colombia and might be associated with a more severe course of bipolar disorder in Low-Middle Income-Countries. We carried out the first case–control study in Colombia using a structural clinical interview and the Childhood Trauma Questionnaire-Short Form (CTQ-SF) to describe the prevalence and association between trauma exposure during childhood with a severe course of illness (early age onset, rapid cycling, ideation or suicide attempt, or ≥ 3 hospitalization) in a sample of BD patients.

Results

A total of 114 cases and 191 controls evaluated showed the following results. Cases included 61.4% BD type I and 38.6% BD type II. The median age was 31.5 years (IQR, 75–24) for BD patients and 31 years old (IQR, 38–24) for healthy controls. A higher prevalence of childhood trauma was evidenced in cases compared to controls. Emotional abuse, physical abuse, sexual abuse, physical neglect and emotional neglect evidenced a strong association with severe bipolar disorder (OR = 3.42, p < .001; OR = 4.68, p < .001; OR = 4.30, p = .003; OR = 5.10, p < .001; OR = 5.64, p < .001, respectively).

Conclusions

This is the first association study between childhood trauma exposure as a higher risk for a severe course of illness in BD patients in Colombian. Our findings highlight the higher prevalence of childhood trauma in bipolar patients and the strong association of childhood trauma with severe bipolar disorder. These findings are relevant for screening and evaluating childhood trauma exposure during the course of BD patients.
Preferred atmospheric circulations associated with favorable prescribed burns in the Gulf of Mexico coast, USA
Authors: Kross Chelsea S. , Rohli Robert V. , Moon Jena A. , Fournier Auriel M. V. , Woodrey Mark S. , Nyman J. Andrew
Published: February 2023

Background

Application of prescribed fire in natural plant communities is an important wildlife habitat management tool. Prescribed fire managers have suggested anecdotally that changing weather patterns may be influencing the frequency of days that have optimal conditions to conduct coastal marsh burns along the US Gulf of Mexico coast. Our study objectives were to (1) determine whether the frequency of atmospheric circulation patterns associated with prescribed fire prescriptions has changed from 1979 to 2018 for the Gulf Coast and (2) identify circulation patterns preferred by land managers for implementing prescribed fire.

Results

While coastal marsh habitat is threatened by climate change and human-associated degradation, weather type frequency was not identified as an important factor related to the application of prescribed fire, as the frequency of weather circulation types has not changed significantly over time (p > 0.05). However, some weather circulation patterns seem more advantageous (e.g., offshore winds) or disadvantageous (e.g., wet cold fronts and high winds) for consideration by prescribed fire applicators across the Gulf.

Conclusions

Further insight into the weather conditions preferred and avoided by land managers along the Gulf of Mexico will improve prediction-based methods for identifying burn windows from weather forecasts. Land managers face many challenges in protecting coastal systems, while also reducing management conflicts (i.e., smoke transport) with local communities. Understanding how constraints such as urbanization, climate change, and sea-level rise interact to affect prescribed fire application will be an increasingly important aspect for developing successful adaptive management plans.
Fibrinogen level among children with liver cirrhosis
Authors: Hosseinabadi Samaneh Hamzelou , Honar Naser , Dehghani Seyed Mohsen , Javaherizadeh Hazhir
Published: February 2023

Introduction

The liver has a major role in the production of coagulation factors, and cirrhotic patients have a series of coagulopathy disorders. The present study aimed to measure plasma fibrinogen levels in children with hepatic cirrhosis.

Method

Patients younger than 18 years old after diagnosis of liver cirrhosis by biopsy were enrolled in the study. Laboratory data including hemoglobin, PT, PTT, INR, and liver function tests were recorded. Fibrinogen levels were measured using the Clauss method. PELD score for children less than 12 years and MELD Na for children over 12 years were used to measure the severity of the liver disease.

Results

Fifty children with cirrhosis were studied. The mean fibrinogen level in the “PELD < 15” group was significantly higher than the other group (P < 0.001). There was no significant relationship between bleeding and fibrinogen levels. There was no significant relationship between PELD and bleeding in subjects (P = 0.87). The results of the study showed neither of these two factors (fibrinogen level and PELD) can play a predictive role in causing hemorrhage in patients.

Conclusion

Our study has shown that fibrinogen level is significantly associated with severity of liver cirrhosis and decreases with more severe disease (PELD levels), but platelet and fibrinogen cannot predict the severity of bleeding in these patients.
Elastic vertically transversely isotropic full-waveform inversion: From synthetic to field data
Authors: He Weiguang , Li Yubing , Liu Lu
Published: February 2023

Representing the earth as an elastic medium leads to a more accurate approximation of the seismic response than can be obtained by assuming an acoustic medium. However, this representation requires a larger number of unknown parameters to be introduced and a more complex seismogram to be considered. Consequently, it is important to carefully deal with two challenging issues, the impact of strong surface waves and the crosstalk among parameters, for land seismic multiparameter full-waveform inversion (FWI). Under the elastic vertically transversely isotropic assumption, a robust FWI approach is developed by combining the optimal transport (OT) misfit function, the Gaussian time window, and the suitable parameterization [Formula: see text]. Without specific preprocessing, surface waves usually dominate the inversion process, leaving the body waves not fully exploited. Correspondingly, the subsurface model is only updated at a shallow depth. The OT misfit function can balance the contributions of surface and body waves to model updates in an automatic manner. In addition, the Gaussian time window further improves the weights of the body waves during inversion. We efficiently exploit the entire seismogram with these two approaches. In this configuration, the performances of several parameterizations chosen from radiation pattern analysis are evaluated. Our inversion strategy is applied to the Middle East model and a field data application. In both cases, it outperforms other inversion strategies. The entire land seismic data are efficiently exploited and multiparameters are simultaneously reconstructed.
Pediatric Neurosurgical Capacity for the Care of Children With CNS Tumors Worldwide: A Cross-Sectional Assessment
Authors: Roach Jordan T. , Qaddoumi Ibrahim , Baticulon Ronnie E. , Figaji Anthony , Campos Danny A. , Arredondo Luis , Boop Frederick A. , Moreira Daniel C.
Published: February 2023

PURPOSE

Efforts to address inequities in the treatment of pediatric CNS tumors and the burden of childhood cancer globally have prompted the designation of low-grade glioma as one of six index cancers for the World Health Organization Global Initiative for Childhood Cancer. Understanding the importance of neurosurgical interventions and evaluating pediatric neurosurgical capacity may identify critical interventions to improve outcomes for children with low-grade glioma and other CNS tumors.

METHODS

An online, cross-sectional survey assessing pediatric neurosurgical practice and capacity was distributed to members of the International Society of Pediatric Neurosurgery. The survey included 36 items covering domains including patient volume, available infrastructure, scope of practice, case distribution, and multidisciplinary care.

RESULTS

Responses from 196 individuals from 61 countries, spanning all WHO regions, were included. Ninety-six (49.0%) were from high-income countries, 57 (29.1%) were from upper-middle–income countries, 42 (21.4%) were from lower-middle–income countries (LMICs), and 1 was (0.5%) from a low-income country. Most respondents had a catchment population of ≥ 1 million and indicated the availability of basic neurosurgical resources such as a dedicated neurosurgical operating theater and surgical microscope. The presence of a neurosurgical intensive care unit, inpatient rehabilitation services, and infection monitoring showed similar availability across country groups. Quantitative scoring of 13 infrastructure and service items established that fewer resources were available in low-income countries/LMICs and upper-middle–income countries compared with high-income countries. The volume of pediatric CNS tumor cases and case distribution did not vary according to World Bank country groups.

CONCLUSION

This study provides a comprehensive evaluation of pediatric neurosurgical capacity across the globe, establishing variability of resources on the basis of the country income level. Our findings suggest that pediatric neurosurgeons in LMICs may benefit from key neurosurgical instrumentation and increased support for multidisciplinary brain tumor programs and childhood cancer research efforts.
Bortezomib-Dexamethasone, Rituximab, and Cyclophosphamide as First-Line Treatment for Waldenström's Macroglobulinemia: A Prospectively Randomized Trial of the European Consortium for Waldenström's Macroglobulinemia
Authors: Buske Christian , Dimopoulos Meletios A. , Grunenberg Alexander , Kastritis Efstathios , Tomowiak Cecile , Mahé Béatrice , Troussard Xavier , Hajek Roman , Viardot Andreas , Tournilhac Olivier , Aurran Therese , Lepretre Stephane , Zerazhi Hacene , Hivert Benedicte , Leblond Veronique , de Guibert Sophie , Brandefors Lena , Garcia-Sanz Ramon , Gomes da Silva Maria , Kimby Eva , Schmelzle Birgit , Kaszynski Dajana , Dreyhaupt Jens , Muche Rainer , Morel Pierre
Published: February 2023

PURPOSE

Rituximab/chemotherapy is a cornerstone of treatment for Waldenström's macroglobulinemia (WM). In addition, bortezomib has shown significant activity in WM. This study evaluated the efficacy and safety of dexamethasone, rituximab, and cyclophosphamide (DRC) as first-line treatment in WM.

METHODS

In this European study, treatment-naïve patients were randomly assigned to DRC or bortezomib-DRC B-DRC for six cycles. The primary end point was progression-free survival. Secondary end points included response rates, overall survival, and safety.

RESULTS

Two hundred four patients were registered. After a median follow-up of 27.5 months, the estimated 24-month progression-free survival was 80.6% (95% CI, 69.5 to 88.0) for B-DRC and 72.8% (95% CI, 61.3 to 81.3) for DRC ( P = .32). At the end of treatment, B-DRC and DRC induced major responses in 80.6% versus 69.9% and a complete response/very good partial response in 17.2% versus 9.6% of patients, respectively. The median time to first response was shorter for B-DRC with 3.0 (95% CI, 2.8 to 3.2) versus 5.5 (95% CI, 2.9 to 5.8) months for DRC. This resulted in higher major response rates (57.0% v 32.5%; P < .01) after three cycles of B-DRC compared with DRC. At best response, the complete response/very good partial response increased to 32.6% for B-DRC. Both treatments were well tolerated: grade ≥ 3 adverse events occurred in 49.2% of all patients (B-DRC, 49.5%; DRC, 49.0%). Peripheral sensory neuropathy grade 3 occurred in two patients treated with B-DRC and in none with DRC.

CONCLUSION

This large randomized study illustrates that B-DRC is highly effective and well tolerated in WM. The data demonstrate that fixed duration immunochemotherapy remains an important pillar in the clinical management of WM.
Impact of Frailty on Health Care Resource Utilization and Costs of Care in Myelodysplastic Syndromes
Authors: Mozessohn Lee , Li Qing , Liu Ning , Leber Brian , Khalaf Dina , Sabloff Mitchell , Christou Grace , Yee Karen , Chodirker Lisa , Parmentier Anne , Siddiqui Mohammed , Mamedov Alexandre , Zhang Liying , Liu Ying , Earle Craig C. , Cheung Matthew C. , Mittmann Nicole , Buckstein Rena
Published: February 2023

PURPOSE:

The role of frailty in affecting survival in myelodysplastic syndromes (MDS) is increasingly recognized. Despite this, a paucity of data exists on the association between frailty and other clinically meaningful outcomes including health care resource utilization and costs of care.

METHODS:

We linked the Ontario subset of the prospective Canadian MDS registry (including baseline patient/disease characteristics) to population-based health system administrative databases. Baseline frailty was calculated from the 15-item MDS-specific frailty scale (FS-15). Primary outcomes were public health care utilization and 30-day standardized costs of care (2019 Canadian dollars) determined for each phase of disease (initial, continuation, and terminal phases). Negative binomial regression was used to assess the association between frailty and health care costs with Poisson regression to explore predictors of hospitalization.

RESULTS:

Among 461 patients with complete FS-15 scores, 374 (81.1%) had a hospitalization with a mean length of stay of 10.6 days. Controlling for age, comorbidities, Revised International Prognostic Scoring System, and transfusion dependence, the FS-15 was independently associated with hospitalization during the initial ( P = .02) and continuation ( P = .01) phases but not the terminal disease phase ( P = .09). The mean 30-day standardized cost per patient was $8,499 (median, $6,295; interquartile range, $2,798-$11,996), largely driven by cancer clinic visits and hospitalization. On multivariable analysis, the FS-15 was independently associated with costs of care during the initial disease phase ( P = .02).

CONCLUSION:

We demonstrate an association between frailty and clinically meaningful outcomes including hospitalization and costs of care in patients with MDS. Our results suggest that baseline frailty may help to inform patients and physicians of expected outcomes.