Miracle-dz/UniFAR-FTUs huggingface dataset:
The Impact of Maternal Adverse Childhood Experiences on Offspring’s Internalizing and Externalizing Problems

Objective Adverse childhood experiences (ACEs) are associated with negative physical and mental health outcomes across the lifespan, but research on intergenerational transmission of maternal ACEs and its impact on the offspring’s mental health problems are limited. The study examines the effects of maternal ACEs on the risk of internalizing or externalizing problems among offspring. Methods There were 450 mother-child dyads. Mothers completed the Adverse Childhood Experiences Questionnaire. The child outcomes included internalizing and externalizing problems assessed by the Korean Child Behavior Checklist (K-CBCL) and Korean Youth Self-Report (K-YSR), depression assessed by the Center for Epidemiological Studies Depression Scale for Children (CES-DC) and anxiety assessed by the Screen for Child Anxiety Related Emotional Disorders (SCARED). Results 36.1% of mothers experienced at least one ACE, and 11.1% experienced three or more ACEs. Cumulative maternal ACEs were associated with internalizing problems, externalizing problems, depression and anxiety in the offspring. Household dysfunction from maternal ACEs was significantly associated with delinquent behavior, anxiety/depression, and somatic complaints in the offspring. Conclusion The findings support the hypothesis that maternal ACEs are related to mental health problems in the offspring. Further research is needed to determine the factors mediating intergenerational transmission as well as intervention strategies to prevent ACEs and mental health problems in the offspring.
Safety and tolerability of linagliptin in Asians with type 2 diabetes: a pooled analysis of 4457 patients from 21 randomized, double-blind, placebo-controlled clinical trials

ABSTRACT Background Safety and tolerability of glucose-lowering drugs is a key consideration for use in type 2 diabetes (T2D). We evaluated the safety and tolerability of the dipeptidyl peptidase-4 inhibitor linagliptin in Asian patients with T2D. Research design and methods This was a post-hoc, descriptive pooled analysis of 21 randomized, double-blind, placebo-controlled clinical trials of linagliptin in T2D patients lasting ≤52 weeks. We evaluated adverse events (AEs) and laboratory parameters in Asian participants living in Asia, both overall and in the East Asian subgroup. Results This analysis included 4457 Asian patients overall (2712 receiving linagliptin; 1745 receiving placebo) and 3057 (68.6%) East Asians. AEs were reported in 1510 (55.7%) Asian patients receiving linagliptin and 1032 (59.1%) receiving placebo but were considered drug-related in only 13.0% of each group. Serious AEs occurred in 109 (4.0%) linagliptin patients and 90 (5.2%) placebo patients. The most common AEs were nasopharyngitis (6.4% linagliptin, 7.3% placebo), upper respiratory tract infection (5.7% linagliptin, 6.5% placebo), and hypoglycemia (7.3% linagliptin, 6.3% placebo). One linagliptin patient had pancreatitis; none had bullous pemphigoid. No clinically relevant mean changes in laboratory parameters occurred. These findings were consistent in East Asians. Conclusions Linagliptin is well tolerated in Asian T2D patients, including East Asians, with low risk for AEs.
Expressing grief through metaphors: family caregivers’ experience of care and grief during the Covid-19 pandemic

ABSTRACT Purpose: The COVID-19 pandemic has disrupted thousands of individuals’ experience of caregiving and grief. This qualitative study aimed to gain in-dept understanding of family caregivers’ lived experiences of caregiving and bereavement in the context of the COVID-19 pandemic in Quebec, Canada. The study also aimed at providing new insight about caregiving and bereavement by analysing the metaphors family caregivers use to report their experiences. Methods: The design of this study was guided by an interpretative phenomenological approach. In-depth interviews were conducted with twenty bereaved family caregivers who had lost a loved one during the first waves of the pandemic. Results: Results indicate that bereaved family caregivers lived and understood their experience in terms of metaphoric cut-offs, obstructions and shockwaves. These three metaphors represented the grief process and the bereaved’s quest for social connection, narrative coherence and recognition. Conclusion: By identifying the meaning of the bereaved’s metaphors and the quest they reveal, our study underlines the singularity of pandemic grief and points to the value and meaning of caregiving with regard to the grieving process.
Hairy cell leukemia 2022: Update on diagnosis, risk‐stratification, and treatment

Hairy cell leukemia (HCL) and HCL‐like disorders, including HCL variant (HCL‐V) and splenic diffuse red pulp lymphoma (SDRPL), are a very heterogeneous group of mature lymphoid B‐cell disorders characterized by the identification of hairy cells, a specific genetic profile, a different clinical course, and the need for appropriate treatment.
Evaluation of standardized performance test methods for biomedical Raman spectroscopy

Abstract. Significance: Raman spectroscopy has emerged as a promising technique for a variety of biomedical applications. The unique ability to provide molecular specific information offers insight to the underlying biochemical changes that result in disease states such as cancer. However, one of the hurdles to successful clinical translation is a lack of international standards for calibration and performance assessment of modern Raman systems used to interrogate biological tissue. Aim: To facilitate progress in the clinical translation of Raman-based devices and assist the scientific community in reaching a consensus regarding best practices for performance testing. Approach: We reviewed the current literature and available standards documents to identify methods commonly used for bench testing of Raman devices (e.g., relative intensity correction, wavenumber calibration, noise, resolution, and sensitivity). Additionally, a novel 3D-printed turbid phantom was used to assess depth sensitivity. These approaches were implemented on three fiberoptic-probe-based Raman systems with different technical specifications. Results: While traditional approaches demonstrated fundamental differences due to detectors, spectrometers, and data processing routines, results from the turbid phantom illustrated the impact of illumination-collection geometry on measurement quality. Conclusions: Specifications alone are necessary but not sufficient to predict in vivo performance, highlighting the need for phantom-based test methods in the standardized evaluation of Raman devices.
Local immune response as novel disease mechanism underlying abdominal pain in patients with irritable bowel syndrome

ABSTRACT Objectives Irritable bowel syndrome (IBS) is the most frequently diagnosed functional gastrointestinal disorder, with a prevalence of up to 25% of the global population. IBS patients suffer from abnormal abdominal pain, or visceral hypersensitivity (VHS), associated with altered bowel habits in the absence of an organic detectable cause. The pathophysiology of the disease is incompletely understood, but the dysregulation of the brain-gut axis is well established in IBS. Methods IBS onset is mainly triggered by infectious gastroenteritis, psychological factors, and dietary factors, but genetic predispositions and intestinal dysbiosis might also play a role. Additionally, immune activation, and particularly chronic mast cell activation, have been shown to underlie the development of abdominal pain in IBS. Results By releasing increased levels of mediators, including histamine, mast cells sensitize enteric nociceptors and lead to VHS development. Â The mechanisms underlying aberrant mast cell activation in IBS are still under investigation, but we recently showed that a local break in oral tolerance to food antigens led to IgE-mediated mast cell activation and food-induced abdominal pain in preclinical models and in IBS patients. Conclusion The concept of food-mediated VHS highlights the potential of therapies targeting upstream mechanisms of mast cell sensitization to treat IBS.
Super-resolution imaging of highly curved membrane structures in giant vesicles encapsulating molecular condensates

Molecular crowding is an inherent feature of the cell interior. Synthetic cells as provided by giant unilamellar vesicles (GUVs) encapsulating macromolecules (polyethylene-glycol and dextran) represent an excellent mimetic system to study membrane transformations associated with molecular crowding and protein condensation. Similarly to cells, such GUVs loaded with macromolecules exhibit highly curved structures such as internal nanotubes. In addition, upon liquid-liquid phase separation as inside living cells, the membrane of GUVs encapsulating an aqueous two-phase system deforms to form apparent kinks at the contact line of the interface between the two aqueous phases. These structures, nanotubes and kinks, have dimensions below optical resolution and if resolved, can provide information about material properties such as membrane spontaneous curvature and intrinsic contact angle describing the wettability contrast of the encapsulated phases to the membrane. Previous experimental studies were based on conventional optical microscopy which cannot resolve these membrane and wetting properties. Here, we studied these structures with super-resolution microscopy, namely stimulated emission depletion (STED) microscopy, together with microfluidic manipulation. We demonstrate the cylindrical nature of the nanotubes with unprecedented detail based on the superior resolution of STED and automated data analysis. The spontaneous curvature deduced from the nanotube diameters is in excellent agreement with theoretical predictions. Furthermore, we were able to resolve the membrane “kink” structure as a smoothly curved membrane demonstrating the existence of the intrinsic contact angle. We find very good agreement between the directly measured values and the theoretically predicted ones based on the apparent contact angles on the micrometer scale. During different stages of cellular events, biomembranes undergo a variety of shape transformations such as the formation of buds and nanotubes regulated by membrane necks. We demonstrate that these highly curved membrane structures are amenable to STED imaging and show that such studies provide important insights in the membrane properties and interactions underlying cellular activities.
Invasion of a Recurrent Laryngeal Nerve from Small, Well-Differentiated Papillary Thyroid Cancers: Patient Selection Implications for Active Surveillance.

Background: The success of an active surveillance management approach to low-risk papillary thyroid cancer (PTC) is heavily dependent on proper patient selection. For example, primary tumors located in a subcapsular position immediately adjacent to the trachea or a recurrent laryngeal nerve (RLN) are considered to be inappropriate for active surveillance. Since pre-operative imaging cannot reliably rule out extrathyroidal extension or reveal the full course of the RLN relative to the thyroid gland, it is important for clinicians to understand subcapsular tumor locations and minimum tumor sizes that are most likely to be associated with gross invasion of the RLNs. Methods: We assessed the medical records of 123 patients treated at Memorial Sloan Kettering Cancer Center (MSK) between 1986 and 2015 who had a primary PTC tumor demonstrating gross extrathyroidal extension to either the right or left RLN. Thirty patients with a primary tumor ≤2 cm in diameter demonstrating extrathyroidal extension into an RLN were included in the analysis. Results: Gross invasion of an RLN by tumors ≤2 cm is a rare event that was seen in only 0.8% (35/4,334) of patients with PTC who underwent initial thyroid surgery at MSK between 1986 and 2015. Gross RLN invasion was associated with subcapsular PTC tumors located in either the right paratracheal area (60%), left paratracheal area (36.7%), or right lateral posterior lobe area not adjacent to the trachea (3.3%). Only a quarter of the patients had imaging findings suggestive of extrathyroidal extension and only 30% had clinically apparent vocal paresis/paralysis on pre-operative examination. Invasion of the RLN was not observed for primary tumors <0.9 cm in diameter, regardless of tumor location. Conclusions: Well-differentiated PTC tumors ≥0.9 cm in maximal diameter which are located in the right paratracheal, left paratracheal, and right lateral posterior lobe subcapsular positions are usually not appropriate for active surveillance even in the absence of definitive evidence for nerve invasion on pre-operative imaging or vocal cord examination. Patient selection for active surveillance management should take into account not only the size and growth rate of a tumor but also its location in relation to the expected course of RLNs.
Assessment of the Anti-Cancer Efficiency of Silver Moringa oleifera Leaves Nano-extract against Colon Cancer Induced Chemically in Rats

Background: Colorectal cancer (CRC) categorized as the most common type of gastrointestinal cancers affected both genders equally. Chemotherapeutic drugs became limited due to their deleterious side effects. Therefore, efficiency of M. oleifera leaves extract increased by incorporating silver nanoparticles (Ag-NPs) then studied against colon cancer induced by azoxymethane (AOM) in rats. Methods: Different hematological and biochemical measurements in addition to specific tumor and inflammatory markers were quantified. Histopathological examination for Colonic tissues was performed. Native proteins and isoenzyme patterns were electrophoretically detected in addition to assaying expression of Tumor Protein P53 (TP53) and Adenomatous Polyposis Coli (APC) genes in colonic tissues. Results: M. oleifera nano-extract restored levels of the hematological and biochemical measurements in addition to levels of tumor and inflammatory markers to normalcy in both of nano-extract simult- and post-treated groups. Also, it minimized severity of the histopathological alterations in the simult-treated group and prevented it completely in the post-treated group. The lowest similarity index (SI%) values were noticed with electrophoretic protein (SI=61.54%), lipid (SI=0.00%) and calcium (SI=75.00%) moieties of protein patterns, catalase (SI=85.71%), peroxidase (SI=85.71%), α-esterase (SI=50.00%) and β-esterase (SI=50.00%) isoenzymes in addition to altering the relative quantities of total protein and isoenzyme bands in colon of cancer induced group. Moreover, levels of TP53 and APC gene expression increased significantly (P≤0.05) in colon cancer induced group. The nano-extract prevented the qualitative and quantitative alterations in the different electrophoretic patterns in addition to restoring levels of the gene expressions to normalcy in both of simult- and post-treated groups. Conclusion: M. oleifera nano-extract exhibited ameliorative effect against the biochemical, physiological and molecular alterations induced by AOM in nano-extract simult- and post-treated groups.
Biocomposite Based on Collagen/Calcium Salts Extraction from Sardine Scales

It is well known that fish scales are composed of collagen covered with calcium salts. In this paper, we report the extraction of biocomposite of collagen and calcium salts from scales of Moroccan sardines for the first time. This biocomposite was extracted from scales of Sardina Pilchardus, in seven steps, using acid solution. The physicochemical studies revealed that obtained biocomposite could have promising applications in the food, medical, pharmaceutical and cosmetic industries.
The impact of Marfan syndrome on an Aboriginal Australian family: ‘I don’t like it as much as I don’t like cancer’

Marfan syndrome (MFS) is an autosomal dominantly inherited connective tissue disorder. Aortic dilatation/dissection and ectopia lentis are the most severe features, which affect physical functioning and psychological well‐being. In Aboriginal Australians, there is little psychosocial research on genetic conditions. This study explored the physical, psychological, and practical impacts of MFS on Aboriginal Australians. Eighteen (8 affected and 10 unaffected) members of a large Aboriginal Australian family with MFS participated in an ethically approved study. Semi‐structured qualitative interviews were conducted, transcribed verbatim, and analyzed thematically. All individuals reported challenges from MFS, negatively affecting day‐to‐day living. Severe vision impairment was perceived as the greatest challenge, contributing to feelings of stigma and exclusion. With aging, concerns shifted toward cardiac complications. The unpredictability of lens dislocation and aortic dissection was reported to be psychologically challenging. Participants described MFS‐related barriers to obtaining and retaining employment, especially following cardiac surgery; with consequential psychological and financial hardships. Participants articulated that their cultural drive to support the ill and respectfully mourn the deceased, regardless of distance, resulted in a significant financial burden. Additionally, when hospitalization and/or funerals occurred, financially solvent individuals were expected to share resources, without any expectation of repayment or reciprocity (i.e., ‘demand sharing’, common in Aboriginal Australian culture). This study documents the nature and pervasiveness of uncertainty for both affected and unaffected members of an MFS family. Many reported challenges are consistent with other MFS cohorts (including stigma, social exclusion, and unemployment). However, our findings suggest that cultural values may exacerbate the financial costs of MFS for Aboriginal Australians.
Update of the Blood Lead Reference Value — United States, 2021

The negative impact of lead exposure on young children and those who become pregnant is well documented but is not well known by those at highest risk from this hazard. Scientific evidence suggests that there is no known safe blood lead level (BLL), because even small amounts of lead can be harmful to a child's developing brain (1). In 2012, CDC introduced the population-based blood lead reference value (BLRV) to identify children exposed to more lead than most other children in the United States. The BLRV should be used as a guide to 1) help determine whether medical or environmental follow-up actions should be initiated for an individual child and 2) prioritize communities with the most need for primary prevention of exposure and evaluate the effectiveness of prevention efforts. The BLRV is based on the 97.5th percentile of the blood lead distribution in U.S. children aged 1-5 years from National Health and Nutrition Examination Survey (NHANES) data. NHANES is a complex, multistage survey designed to provide a nationally representative assessment of health and nutritional status of the noninstitutionalized civilian adult and child populations in the United States (2). The initial BLRV of 5 μg/dL, established in 2012, was based on data from the 2007-2008 and 2009-2010 NHANES cycles. Consistent with recommendations from a former advisory committee, this report updates CDC's BLRV in children to 3.5 μg/dL using NHANES data derived from the 2015-2016 and 2017-2018 cycles and provides helpful information to support adoption by state and local health departments, health care providers (HCPs), clinical laboratories, and others and serves as an opportunity to advance health equity and environmental justice related to preventable lead exposure. CDC recommends that public health and clinical professionals focus screening efforts on populations at high risk based on age of housing and sociodemographic risk factors. Public health and clinical professionals should collaborate to develop screening plans responsive to local conditions using local data. In the absence of such plans, universal BLL testing is recommended. In addition, jurisdictions should follow the Centers for Medicare & Medicaid Services requirement that all Medicaid-enrolled children be tested at ages 12 and 24 months or at age 24-72 months if they have not previously been screened (3).
Hydroalcoholic leaves extract of Vaccinium ashei Reade promotes cell cycle arrest and apoptosis on T-cell acute lymphoblastic leukemia

Abstract Vaccinium ashei Reade, popularly known as Rabbiteye blueberry, has several therapeutic properties attributed to the phenolic compounds present in its leaves and fruits. Here, we sought to evaluate the effects of the hydroalcoholic extract from V. ashei leaves (Bluegem cultivar, VAB) in T-cell Acute lymphoblastic leukemia (T-ALL). The VAB extract was toxic to T-ALL cells at the ∼60 µg/ml concentration. T-ALL cell death occurred through apoptosis. VAB extract was found to induce micronuclei formation, p53 pathway activation, and cell cycle arrest. Those mutagenic effects were evidenced through microscopy analysis and molecular p53 pathway activation. A series of phenolic compounds were identified in VAB extract by mass spectrometry, such as vanillic acid, catechin, caffeic acid, chlorogenic acid, rutin, coumaric acid, taxifolin, quercetin and naringenin, some of which are presumed to induce DNA damage. In conclusion, the V. ashei leaves extract may have important secondary metabolites with antileukemic properties. Graphical Abstract
Is there an effective dose of aerobic exercise associated with better executive function in youth with attention deficit hyperactivity disorder?

ABSTRACT Attention-deficit/hyperactivity disorder (ADHD) is the most prevalent neurodevelopmental disorder in children, and it’s linked to a higher risk of academic failure, interpersonal issues, mental illness, and criminality. Despite several of the comparative and detailed reviews on the effects of ADHD interventions on core symptoms, there is no data summarizing the effects of aerobic exercise (AE) on executive functions (EFs). Therefore, this study aimed to systematically review and determine the relationship between AE (acute and chronic) dosage and EFs (attention, inhibition, set-shifting, and working memory) in youth with ADHD. The consideration of how AE dosage impacts aspects of EFs has not been investigated in detail previously. The study adhered to PRISMA guideline. Sixdatabases were searched without any date restrictions, up to February 2021, for articles relating to AE interventions to influence EFs in youth with ADHD 18 years old. Quality assessment of the reviewed papers was addressed. Thirteen studies met the inclusion criteria. Improvements in all aspects of EFs were reported after children with ADHD engaged in acute AE lasting 20–30 minutes with at least moderate intensity (65% ≤ 80% HRmax). Furthermore, chronic exercise that lasts at least 45 minutes and in the range of moderate tohigh intensity (i.e., 60% ≤ 75% HRmax), 3 days/week for 6–12, elicits additional benefits in inhibition and set-shifting.Different dosage of AE might differently influence aspects of EFs; however, this finding rests on preliminary evidence at this stage and thus should be treated with caution.It is necessary to establish suitable interventions with regard to the dosage of AE types to improve EFs in young people with ADHD.