Miracle-dz/UniFAR-FTUs huggingface dataset:
Beyond circadian rhythms: Emerging roles of ultradian rhythms in control of liver functions.

The mammalian liver must cope with various metabolic and physiological changes that normally recur every day and primarily stem from daily cycles of rest-activity and fasting-feeding. While large body of evidence supports the reciprocal regulation of circadian rhythms and liver function, the research on the hepatic ultradian rhythms have largely been lagging behind. However, with the advent of more cost-effective high-throughput omics technologies, high-resolution time-lapse imaging, and more robust and powerful mathematical tools, several recent studies have shed new light on the presence and functions of hepatic ultradian rhythms. In this review, we will first very briefly discuss the basic principles of circadian rhythms, and then cover in greater details the recent literature related to ultradian rhythms. Specifically, we will highlight the prevalence and mechanisms of hepatic 12-hour rhythms, and 8-hour rhythms, which cycle at the second and third harmonics of circadian frequency. Finally, we also refer to ultradian rhythms with other frequencies and examine the limitations of the current approaches as well as the challenges related to identifying ultradian rhythm and addressing their molecular underpinnings.
The Role of Visual Experience in Individual Differences of Brain Connectivity

Visual cortex organization is highly consistent across individuals. But to what degree does this consistency depend on life experience, in particular sensory experience? In this study, we asked whether visual cortex reorganization in congenital blindness results in connectivity patterns that are particularly variable across individuals, focusing on resting-state functional connectivity (RSFC) patterns from the primary visual cortex. We show that the absence of shared visual experience results in more variable RSFC patterns across blind individuals than sighted controls. Increased variability is specifically found in areas that show a group difference between the blind and sighted in their RSFC. These findings reveal a relationship between brain plasticity and individual variability; reorganization manifests variably across individuals. We further investigated the different patterns of reorganization in the blind, showing that the connectivity to frontal regions, proposed to have a role in the reorganization of the visual cortex of the blind toward higher cognitive roles, is highly variable. Further, we link some of the variability in visual-to-frontal connectivity to another environmental factor—duration of formal education. Together, these findings show a role of postnatal sensory and socioeconomic experience in imposing consistency on brain organization. By revealing the idiosyncratic nature of neural reorganization, these findings highlight the importance of considering individual differences in fitting sensory aids and restoration approaches for vision loss. SIGNIFICANCE STATEMENT The typical visual system is highly consistent across individuals. What are the origins of this consistency? Comparing the consistency of visual cortex connectivity between people born blind and sighted people, we showed that blindness results in higher variability, suggesting a key impact of postnatal individual experience on brain organization. Further, connectivity patterns that changed following blindness were particularly variable, resulting in diverse patterns of brain reorganization. Individual differences in reorganization were also directly affected by nonvisual experiences in the blind (years of formal education). Together, these findings show a role of sensory and socioeconomic experiences in creating individual differences in brain organization and endorse the use of individual profiles for rehabilitation and restoration of vision loss.
Impact of breakthrough COVID-19 cases during the omicron wave on vascular health and cardiac autonomic function in young adults

We and others have previously shown that COVID-19 results in vascular and autonomic impairments in young adults. However, the newest variant of COVID-19 (Omicron) appears to have less severe complications. Therefore, we investigated whether recent breakthrough infection with COVID-19 during the Omicron wave impacts cardiovascular health in young adults. We hypothesized that measures of vascular health and indices of cardiac autonomic function would be impaired in those who had the Omicron variant of COVID-19 when compared with controls who never had COVID-19. We studied 23 vaccinated adults who had COVID-19 after December 25, 2021 (Omicron; age, 23 ± 3 yr; 14 females) within 6 wk of diagnosis compared with 13 vaccinated adults who never had COVID-19 (age, 26 ± 4 yr; 7 females). Macro- and microvascular function were assessed using flow-mediated dilation (FMD) and reactive hyperemia, respectively. Arterial stiffness was determined as carotid-femoral pulse wave velocity (cfPWV) and augmentation index (AIx). Heart rate (HR) variability and cardiac baroreflex sensitivity (BRS) were assessed as indices of cardiac autonomic function. FMD was not different between control (5.9 ± 2.8%) and Omicron (6.1 ± 2.3%; P = 0.544). Similarly, reactive hyperemia (P = 0.884) and arterial stiffness were not different between groups (e.g., cfPWV; control, 5.9 ± 0.6 m/s and Omicron, 5.7 ± 0.8 m/s; P = 0.367). Finally, measures of HR variability and cardiac BRS were not different between groups (all, P > 0.05). Collectively, these data suggest preserved vascular health and cardiac autonomic function in young, otherwise healthy adults who had breakthrough cases of COVID-19 during the Omicron wave. NEW & NOTEWORTHY We show for the first time that breakthrough cases of COVID-19 during the Omicron wave does not impact vascular health and cardiac autonomic function in young adults. These are promising results considering earlier research showing impaired vascular and autonomic function following previous variants of COVID-19. Collectively, these data demonstrate that the recent Omicron variant is not detrimental to cardiovascular health in young, otherwise healthy, vaccinated adults.
Anesthetic Challenges in a Patient With TANGO2 Gene Deletion, DiGeorge Syndrome, and Tetralogy of Fallot: A Case Report

Mutations of the transport and Golgi organization 2 (TANGO2) genes are linked with both long-term neurological decline and acute metabolic crises during stress, leading to significant anesthetic risk. Crises are marked by rhabdomyolysis, lactic acidosis, seizures, cardiac dysfunction, and dysrhythmias. Much is unknown about optimal management of this condition, especially in the acute and critical care settings. The following report describes the anesthetic challenges of a patient with simultaneous TANGO2 gene deletion, DiGeorge Syndrome, and Tetralogy of Fallot, who presented for an interventional cardiac procedure with the goal of metabolic crisis-avoidance and facilitation of safe but expeditious recovery and discharge home.
Comparative reproductive biology of pre-, imaginal, and neotenic castes of the Asian termite Coptotermes gestroi (Blattaria, Isoptera, Rhinotermitidae)

Abstract The Asian subterranean termite Coptotermes gestroi is a worldwide structural pest, although its reproductive biology has been poorly investigated due to a cryptic habit and occurrence of polycalic nests. In this study, we investigated ovarian development and oogenesis in different-aged females of C. gestroi: fourth-instar nymphs, non-functional neotenics, alates, and functional queens. We show that the ovaries develop gradually according to their age and functionality, as younger individuals possess immature oocytes, whereas alates and functional queens always undergo vitellogenesis. Oocytes were classified into previtellogenic (stages I, II, and III) or vitellogenic (stages IV, V, and VI). Ovary development varied among non-functional neotenics, and a rapid differentiation and/or the presence of primary reproductives are believed to influence such a maturation. Immature oocyte stages were shared between fourth-instar nymphs and neotenics. These characteristics, together with other neotenic features (wing buds, body pigmentation, and eye color), should be evaluated in detail aiming to clarify which nymphal instars differentiate into secondary reproductives. Oogenesis was not uniform among alate females, and cross-sectional area of terminal oocytes was significantly smaller in alates when compared to functional queens, suggesting different degrees of maturation in swarming individuals. Functional queens always had mature terminal oocytes (stage VI). Ovariole number and oocyte maturation in C. gestroi relies on several factors and may therefore differ among individuals of the same caste. Future studies should take into account these reproductive features to evaluate how they impact colony development.
When Is Mass Prophylaxis Cost-Effective for Epidemic Control? A Comparison of Decision Approaches

Background For certain communicable disease outbreaks, mass prophylaxis of uninfected individuals can curtail new infections. When an outbreak emerges, decision makers could benefit from methods to quickly determine whether mass prophylaxis is cost-effective. We consider 2 approaches: a simple decision model and machine learning meta-models. The motivating example is plague in Madagascar. Methods We use a susceptible-exposed-infectious-removed (SEIR) epidemic model to derive a decision rule based on the fraction of the population infected, effective reproduction ratio, infection fatality rate, quality-adjusted life-year loss associated with death, prophylaxis effectiveness and cost, time horizon, and willingness-to-pay threshold. We also develop machine learning meta-models of a detailed model of plague in Madagascar using logistic regression, random forest, and neural network models. In numerical experiments, we compare results using the decision rule and the meta-models to results obtained using the simulation model. We vary the initial fraction of the population infected, the effective reproduction ratio, the intervention start date and duration, and the cost of prophylaxis. Limitations We assume homogeneous mixing and no negative side effects due to antibiotic prophylaxis. Results The simple decision rule matched the SEIR model outcome in 85.4% of scenarios. Using data for a 2017 plague outbreak in Madagascar, the decision rule correctly indicated that mass prophylaxis was not cost-effective. The meta-models were significantly more accurate, with an accuracy of 92.8% for logistic regression, 95.8% for the neural network model, and 96.9% for the random forest model. Conclusions A simple decision rule using minimal information about an outbreak can accurately evaluate the cost-effectiveness of mass prophylaxis for outbreak mitigation. Meta-models of a complex disease simulation can achieve higher accuracy but with greater computational and data requirements and less interpretability. Highlights We use a susceptible-exposed-infectious-removed model and net monetary benefit to derive a simple decision rule to evaluate the cost-effectiveness of mass prophylaxis. We use the example of plague in Madagascar to compare the performance of the analytically derived decision rule to that of machine learning meta-models trained on a stochastic dynamic transmission model. We assess the accuracy of each approach for different combinations of disease dynamics and intervention scenarios. The machine learning meta-models are more accurate predictors of mass prophylaxis cost-effectiveness. However, the simple decision rule is also accurate and may be a preferred substitute in low-resource settings.
The Heritability of Twinning in Seven Large Historic Pedigrees

Abstract It is widely recognized that dizygotic twinning (DZT) runs in families, but estimates of heritability from twin and family data are remarkably scarce and vary considerably. Here, we traced seven large, sometimes historical, multigeneration pedigrees from West Africans, fin de siècle French Jews, Canadians (two pedigrees), and the French royal family, in which twin births were recorded. We estimated heritability of twinning (of all types) as zygosity information was not available, diluting the true DZT heritability by a third or so. The estimates in the range 8−20% are remarkably consistent across time (8−19 generations) and ethnicities and also consistent with twin and family estimates.
Salvage of Chronic Therapy‐Resistant Bilateral Charcot Foot Osteoarthropathy with Signs of Osteomyelitis

Charcot arthropathy is an insidious condition affecting the lower limbs of diabetic patients. It is a complication of diabetic neuropathy resulting from subsequent Wallerian degeneration of the nerves. This complication may eventually lead to limb amputation and a poor patient prognosis if not diagnosed and treated successfully. Herein, we report the case of a 73‐year‐old female who presented with rapidly progressive bilateral Charcot foot over a 5‐week period, necessitating an exostectomy on the mid foot, specifically on the cuboid bone and the navicular cuneiform joint. Her presentation with rapidly progressing foot ulcers on the plantar aspect prompted initial treatment based on osteomyelitis. The report will therefore serve as a useful guide on how to properly treat Charcot foot, which may present in an atypical manner.
Association of different kinds of obesity with diabetic retinopathy in patients with type 2 diabetes

Introduction Although obesity is one of the established risk factors of diabetes mellitus, the relationship between obesity and diabetic retinopathy (DR) remains unclear in different studies. This study aimed to investigate the association of DR with four obesity-related indexes, including body mass index (BMI), waist to hip ratio (WHR), waist to height ratio (WHtR) and body adiposity index (BAI) in patients with diabetes. Research design and methods We prospectively enrolled 2305 patients with diabetes (2305 eyes) in the Guangzhou Diabetic Eye Study between November 2017 and December 2019 to investigate the prevalence and the association of different types of obesity with DR using BMI, WHR, WHtR and BAI. DR, diabetic macular oedema (DME) and vision-threatening DR (VTDR) were selected as primary outcomes. BMI was categorised as normal (18.5–22.9 kg/m2), overweight (23.0–25.0 kg/m2) and obese (>25.0 kg/m2); WHR, WHtR and BAI were categorised into quarters. Results A total of 336 (14.58%), 93 (4.03%) and 98 (4.25%) developed DR, DME and VTDR, respectively. The prevalence of DR, DME and VTDR was higher in patients with higher BMI/WHR or lower WHtR/BAI. In the univariate regression model, WHR correlated positively with DR, while WHtR and BAI correlated negatively with DR, DME and VTDR. The association remained independent of age, sex and lipid metabolism parameters. In the multivariate model, obese presented as a protective factor for DME and VTDR, while the second quarter of WHtR(Q2-WHtR) presented as a risk factor. Conclusions As high as 67.8% of patients with diabetes were overweight or obese. Obese presented as a significant protective factor of VTDR, while Q2-WHtR presented as a significant risk factor. Therefore, more attention should be paid to centripetal obesity as well as general obesity. Further research is also needed to focus on the improvement of sex-specific weight management in patients with diabetes.
Association between pre-conceptional carbohydrate quality index and the incidence of gestational diabetes: the SUN cohort study

Abstract The aim of the study was to investigate the association between pre-gestational carbohydrate quality index (CQI) and the incidence of gestational diabetes mellitus (GDM). Data from the ‘Seguimiento Universidad de Navarra’ (SUN) cohort were used, which includes 3827 women who notified at least one pregnancy between December 1999 and December 2019. We used a validated semi-quantitative 136-item FFQ to evaluate dietary exposures at baseline and at 10-year follow-up. The CQI was defined by four criteria: glycaemic index, whole-grain/total-grain carbohydrate, dietary fibre intake and solid/total carbohydrate ratio. We fitted generalised estimating equations with repeated measurements of the CQI to assess its relationship with incident GDM. A total of 6869 pregnancies and 202 new cases of incident GDM were identified. The inverse association between the global quality of carbohydrate and the development of GDM was not statistically significant: OR the highest v. the lowest CQI category: 0·67, 95 % CI (0·40, 1·10), Pfor trend = 0·10. Participants at the highest CQI category and with daily carbohydrate amounts ≥50 % of total energy intake had the lowest incidence of GDM (OR = 0·29 (95 % CI (0·09, 0·89)) compared with those with the lowest quality (lowest CQI) and quantity (≤40 %). Further studies are needed to overcome the limitations of our study. Those studies should jointly consider the quality and the quantity of dietary carbohydrates, as the quality might be of importance, especially in women with a higher intake of carbohydrates.
Degradation of pesticides in wheat flour during noodle production and storage

Abstract The fate of five pesticides comprising triadimefon, imidacloprid, fenitrothion, chlorpyrifos-methyl, and chlorpyrifos in wheat flour during noodle production and accelerated storage was systematically investigated. Pesticide residues were determined by high-performance liquid chromatography with diode array detection (HPLC-DAD) after each processing step and accelerated storage. The results indicated that dough mixing reduced the concentration of five pesticide residues by 23–42%, mainly owing to the increase of moisture content. Dough resting had little effect on the residues of triadimefon, imidacloprid, and fenitrothion, but decreased chlorpyrifos-methyl and chlorpyrifos significantly by 24% and 15%, respectively. The pesticide residues increased by 3% to 69% during the drying step, attributed to the different role played by thermal evaporation or thermal degradation and concentration of the different pesticides. Boiling lowered the pesticide residues significantly by 56% to 74% in both fresh noodles and dried noodles. All the pesticide residues decreased during accelerated storage, especially for fenitrothion, chlorpyrifos-methyl, and chlorpyrifos. The processing factors (PFs) of the five pesticides in the drying step were greater than 1, while the others were all less than 1. The whole process for noodle production was beneficial to reduce the pesticide residues with PFs ranging from 0.15 to 0.35. The PFs of five pesticides in accelerated storage were all below 1.
Challenges and opportunities for breast cancer early detection among rural dwelling women in Segamat District, Malaysia: A qualitative study

Introduction Breast cancer patients in low- and middle-income countries often present at an advanced stage. This qualitative study elicited views regarding the challenges and opportunities for breast cancer screening and early detection among women in a low-income semi-rural community in Segamat district, Malaysia. Methods Individual semi-structured interviews with 22 people (health professionals, cancer survivors, community volunteers and member from a non-governmental organization) and four focus group discussions (n = 22 participants) with women from a local community were conducted. All participants were purposively sampled and female residents registered with the South East Asia Community Observatory aged ≥40 years were eligible to participate in the focus group discussions. Data were transcribed verbatim and analyzed using thematic analysis. Results The thematic analysis illuminated barriers, challenges and opportunities across six domains: (i) personal experiences and barriers to help-seeking as well as financial and travel access barriers; (ii) primary care challenges (related to delivering clinical breast examination and teaching breast-self-examination); (iii) secondary care challenges (related to mammogram services); (iv) disconnection between secondary and primary care breast cancer screening pathways; and (v) opportunities to improve breast cancer early detection relating to community civil service society activities (i.e. awareness raising, support groups, addressing stigma/embarrassment and encouraging husbands to support women) and vi) links between public healthcare personnel and community (i.e. improving breast self-examination education, clinical breast examination provision and subsidised mammograms). Conclusion The results point to a variety of reasons for low uptake and, therefore, to the complex nature of improving breast cancer screening and early detection. There is a need to adopt a systems approach to address this complexity and to take account of the socio-cultural context of communities in order, in turn, to strengthen cancer control policy and practices in Malaysia.
Very low rate of humoral response after a third COVID-19 vaccine dose in patients with autoimmune diseases treated with rituximab and non-responders to two doses

Patients with autoimmune diseases (AIDs) treated with rituximab (RTX) are at increased risk of death from COVID- 19 infection. They have a diminished humoral response despite a preserved T- cell response to two doses of mRNA COVID- 19 vaccines. 1 2 It is currently not established how efficient the third dose is in this population. The objective of this study was to assess the effect of a third dose of COVID- 19 vaccine on the
The MNU Plus Testosterone Rat Model of Prostate Carcinogenesis

Animal models of prostate cancer are essential to identify chemopreventive treatments against this major male malignancy. The N-methyl-N-nitrosourea (MNU) plus testosterone rat model of prostate carcinogenesis is a reliable animal model that recapitulates human prostate cancer in many respects and has been used extensively in chemoprevention studies with good predictive value for the results of human clinical trials. The objective of this article is to describe the induction protocol of this model, demonstrate its robustness and reproducibility over time and across rat strains, provide diagnostic criteria for the identification of prostate lesions, and present the current tumor induction protocol so that others can use this model in a reliable manner. The majority of accessory sex gland tumors in this model are adenocarcinomas originating in the anterior and dorsolateral prostate that metastasize to lungs and abdominal structures. The rat strain used is of critical importance, with the commercially available Wistar WU and Fischer F344 strains yielding the highest tumor incidences. Low dose, long-term testosterone treatment is essential for a high tumor incidence, but in advanced stage, large adenocarcinomas do not appear to be androgen dependent. This rat model is a robust and reproducible prostate cancer animal model of human prostate cancer.
Catheter ablation for atrial fibrillation in the elderly >75 years old: Systematic review and meta‐analysis

Atrial fibrillation (AF) ablation is increasingly performed worldwide. As comfort with AF ablation increases, the procedure is increasingly used in patients that are older and in those with more comorbidities. However, it is not well established whether AF ablation in the elderly, especially those >75 years old, has comparable safety and efficacy to younger populations.