Miracle-dz/UniFAR-FTUs huggingface dataset:
Old-age-induced obesity reversed by a methionine-deficient diet or oral administration of recombinant methioninase-producing Escherichia coli in C57BL/6 mice

Obesity increases with aging. Methionine restriction affects lipid metabolism and can prevent obesity in mice. In the present study we observed C57BL/6 mice to double their body weight from 4 to 48 weeks of age and become obese. We evaluated the efficacy of oral administration of recombinant-methioninase (rMETase)-producing E. coli (E. coli JM109-rMETase) or a methionine-deficient diet to reverse old-age-induced obesity in C57BL/6 mice. Fifteen C57BL/6 male mice aged 12–18 months with old-age-induced obesity were divided into three groups. Group 1 was given a normal diet supplemented with non-recombinant E. coli JM109 cells orally by gavage twice daily; Group 2 was given a normal diet supplemented with recombinant E. coli JM109-rMETase cells by gavage twice daily; and Group 3 was given a methionine-deficient diet without treatment. The administration of E. coli JM109-rMETase or a methionine-deficient diet reduced the blood methionine level and reversed old-age-induced obesity with significant weight loss by 14 days. There was a negative correlation between methionine levels and negative body weight change. Although the degree of efficacy was higher in the methionine-deficient diet group than in the E. coli JM109-rMETase group, the present findings suggested that oral administration of E. coli JM109-rMETase, as well as a methionine-deficient diet, are effective in reversing old-age-induced obesity. In conclusion, the present study provides evidence that restricting methionine by either a low-methionine diet or E. coli JM109-rMETase has clinical potential to treat old-age-induced obesity.
NOTES AND CORRESPONDENCE A Form of Potential Vorticity Equation for Depth-Integrated Flow with a Free Surface

A form of linear, barotropic potential vorticity equation is derived for an ocean with a free surface, in which only one scalar variable appears (ocean bottom pressure, or subsurface pressure). Unlike quasigeostrophic or rigid-lid derivations, the only approximation made (apart from linearization) is that changes in the circulation must be slow compared with the inertial frequency. Effects of stratification are included, but only parametrically in the sense that density is treated as a given quantity or forcing term rather than a variable.
Long-Term Intake of Linezolid Elevates Drug Exposure and Reduces Drug Clearance and Elimination in Adults With Drug-Resistant Pulmonary Tuberculosis

Purpose: Pharmacokinetic (PK) studies are critical for dose optimization, and there is a paucity of linezolid (LZD) PK data for prolonged use in drug-resistant tuberculosis (DR-TB). Therefore, the authors evaluated the pharmacokinetics of LZD at two-time intervals in DR-TB during long-term use. Methods: PK evaluation of LZD was performed at the end of the 8th and 16th weeks of treatment in a randomly selected subset of adult pre-extensively drug-resistant pulmonary tuberculosis patients (n = 18) from a multicentric interventional study (Building Evidence to Advance Treatment of TB/BEAT study; CTRI/2019/01/017310), wherein a daily dose of 600 mg LZD was used for 24 weeks. Plasma LZD levels were measured using a validated high-pressure liquid chromatography (HPLC) method. Results: The LZD median plasma Cmax was comparable between the 8th and 16th weeks [18.3 mg/L, interquartile range (IQR: 15.5–20.8 and 18.8 mg/L, IQR: 16.0–22.7, respectively)]. However, the trough concentration increased significantly in the 16th week (3.16 mg/L, IQR: 2.30–4.76), compared with the 8th week (1.98 mg/L, IQR: 0.93–2.75). Furthermore, compared with the 8th week, in the 16th week, there was a significant increase in drug exposure (AUC0-24 = 184.2 mg*h/L, IQR: 156.4–215.8 versus 233.2 mg*h/L, IQR: 187.9–277.2), which corroborated with a longer elimination half-life (6.94 hours, IQR: 5.55–7.99 versus 8.47 hours, IQR:7.36–11.35) and decreased clearance (2.91 L/h, IQR: 2.45–3.33 versus 2.19 L/h, IQR: 1.49–2.78). Conclusions: Long-term daily intake of 600 mg LZD resulted in a significant elevation in trough concentration (>2.0 mg/L) in 83% of the study participants. Furthermore, increased LZD drug exposure may be partly because of decreased clearance and elimination. Overall, the PK data underscore the need for dose adjustment when LZDs are intended for long-term treatment.
Adjunctive systemic antibiotic effect on periodontal state, salivary enzyme activity, and glycemia imbalance in type-2 diabetics after non-surgical periodontal management

ABSTRACT Aim: The current study aimed at analyzing the effect of non-surgical periodontal treatment accompanied by systemic antibiotics on salivary enzyme activities, periodontal parameters, and glycemic control in type−2 diabetic (T2D) patients with chronic periodontitis. Methods: The study included 125 type−2 diabetic patients with chronic periodontitis who had good glycemic control (T2Dc), 125 type−2 diabetics who had bad glycemic control (T2Dpc). The 125 T2Dpc were divided randomly into two groups. The first one enrolled 63 T2Dpc and received a non-surgical periodontal treatment (T2Dpc + NST). The second group enrolled 62 T2Dpc and received the non-surgical treatment accompanied by systemic antibiotics (T2Dpc+NST+A). HbA1c, periodontal indices, and salivary enzyme activities were assessed for all groups. The Glycated hemoglobin (HbA1c) was assessed. The Salivary alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransaminase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) activities were measured. Results: The T2Dpc were characterized by the highest probing depth (PPD) and clinical attachment loss (CAL) periodontal scores, as well as ALP, AST, and ALT enzymatic activities. However, BOP did not differ significantly between T2Dc and T2Dpc. Whereas the rest of clinical parameters PI, GI, and OHI-S did not significantly differ between groups. The Pearson’s analysis revealed three correlations between ALP-PPD, ALP-CAL, and ALP-BOP (bleeding on probing) in both T2Dc and T2Dpc (P < 0.05). Interestingly, a significant decrease in periodontal indices, salivary enzyme activities, and HbA1c was recorded in T2Dpc+NST+A group. Conclusion: The increase in ALP, AST, and ALT activities reflects the impact of uncontrolled T2D on periodontal tissue alteration. The ALP activity increase was associated with the severity of periodontal status in diabetic patients. In comparison to non-surgical treatment alone, the adjunct use of systemic antibiotics improves periodontal state, enzyme activity, and glycemic control.
Lymphocyte Depleting and Modulating Therapies for Chronic Lung Allograft Dysfunction

Chronic lung rejection, also called chronic lung allograft dysfunction (CLAD), remains the major hurdle limiting long-term survival after lung transplantation, and limited therapeutic options are available to slow the progressive decline in lung function. Most interventions are only temporarily effective in stabilizing the loss of or modestly improving lung function, with disease progression resuming over time in the majority of patients. Therefore, identification of effective treatments that prevent the onset or halt progression of CLAD is urgently needed. As a key effector cell in its pathophysiology, lymphocytes have been considered a therapeutic target in CLAD. The aim of this review is to evaluate the use and efficacy of lymphocyte depleting and immunomodulating therapies in progressive CLAD beyond usual maintenance immunosuppressive strategies. Modalities used include anti-thymocyte globulin, alemtuzumab, methotrexate, cyclophosphamide, total lymphoid irradiation, and extracorporeal photopheresis, and to explore possible future strategies. When considering both efficacy and risk of side effects, extracorporeal photopheresis, anti-thymocyte globulin and total lymphoid irradiation appear to offer the best treatment options currently available for progressive CLAD patients. Significance Statement Effective treatments to prevent the onset and progression of chronic lung rejection after lung transplantation are still a major shortcoming. Based on existing data to date, considering both efficacy and risk of side effects, extracorporeal photopheresis, anti-thymocyte globulin, and total lymphoid irradiation are currently the most viable second-line treatment options. However, it is important to note that interpretation of most results is hampered by the lack of randomized controlled trials.
An update on pharmacotherapy for recurrent depression in 2022

ABSTRACT Introduction Major depressive disorder remains a major challenge due to its biopsychosocial burden with increased morbidity and mortality. Despite successful treatment options for the acute episode, recurrence rates are high, on average four times in a life span. Areas covered Both pharmacological as non-pharmacological evidence-based therapeutic options to prevent and treat recurrent depression are discussed. Expert opinion Although some risk factors for recurrence are well known, better evidence is needed. Antidepressant medication should be continued after acute treatment at its full therapeutic dose for longer periods, at least 1 year. There are no clear differences between classes of antidepressant medication when treatment is focused on preventing relapse. Bupropion is the only antidepressant with a proven efficacy to prevent recurrence in seasonal affective disorder. Recent findings conclude maintenance subanesthetic ketamine and esketamine treatment can be effective in sustaining antidepressant effect following remission. Furthermore, the pharmacological approach must be integrated with lifestyle interventions, especially aerobic exercise. Finally, combining pharma- and psychotherapy seems to improve outcome. Network and complexity sciences will help to decrease the high recurrence rates of MDD by developing more integrative and personalized approaches.
Some results on lotto designs

Given parameters n, k, p, t, an (n, k, p, t ) Lotto design is a collection of k-sets, such that any arbitrary p-set, which are chosen from an n-set, intersects at least one k-set in the collection in at least t elements. The number L(n, k, p, t) is size of the minimal (n, k, p, t) Lotto design. We provide constructions and techniques for determining upper and lower bounds for L(n, k, p, t). We also provide computer programs that generate upper bounds for L (n, k, p, t).
Assessment of motor and process skills in Danish occupational therapy practice

Abstract Background The demand for employment of standardized evaluations is increasing. In Denmark, approximately 25% of all occupational therapists (OTs) are trained to use the standardized occupational therapy instrument Assessment of Motor and Process Skills (AMPS). Aims To investigate the use of AMPS within Danish occupational therapy practice and determine factors supporting or hindering the use. Material and methods An online cross-sectional survey was conducted among OTs from various settings. Results Overall, 844 calibrated OTs participated in the survey. Of these, 540 (64%) met the inclusion criteria and 486 (90%) completed the questionnaire. Forty percent of the participants used the AMPS in a standardized way during a one-month period and 56% reported being dissatisfied with the low number of AMPS evaluations completed. Five supporting and nine hindering factors were found to significantly influence the use of standardized AMPS evaluations. Conclusions/Significance Despite demands for standardized evaluations, the AMPS is not regularly used in a standardized way within Danish occupational therapy practice. Use of AMPS in clinical practice seems to be facilitated by an acknowledgement from the management and the OT’s ability to develop habits and routines. Time restraints were reported, however, time to conduct evaluations was not a statistically significant influencing factor.
Robust control of a mobile robot system with kinematic disturbances

Presents the design of a differentiable, robust tracking controller for a mobile robot system. The controller provides robustness with regard to a bounded disturbance that violates the nonholonomic pure rolling and non-slipping constraint. Through the use of a dynamic oscillator and a Lyapunov-based stability analysis, we demonstrate that the position and orientation tracking errors exponentially converge to a neighborhood about zero that can be made arbitrarily small (i.e., the controller ensures that the tracking error is globally uniformly ultimately bounded, GUUB). In addition, we illustrate how the proposed tracking controller can also be utilized to achieve GUUB regulation to an arbitrary desired setpoint. Simulation results are presented to demonstrate the performance of the proposed controller.
A comparison of web and paper based approaches for idea generation

Seven tutorial classes of first year students participated in the study. In the experiment, students were allocated into one of two groups: a web based group or a paper based group. Students were asked two 7-point Likert scale questions in a pre-experiment questionnaire regarding the extent they use electronic and paper materials while studying. Students from each group were then given an introduction to the Su-Field Analysis methodology via a 15 minute instructional video. Participants were presented with an engineering related problem and were provided with 16 minutes of time to independently produce as many solution ideas as possible. Three assessors (the authors) individually reviewed and counted the number of ideas generated by students. The average number of ideas generated within each group was used to determine which group was most effective at idea generation. The mean values of the Likert scale questions from the pre-experiment questionnaire were compared. The difference between the values suggested that the engineering students perceive that they utilise electronic materials to a greater extent than paper based materials whilst studying. A Wilcoxon Singed Ranks Test was performed to determine whether the difference between means was statistically significant. The results of the test established that there was statistical significance between the mean values. Participants from the paper based group generated 10.5 ideas on average, while participants of the web based group generated an average of 7.9 ideas. The distribution of the number of generated ideas for each group was checked for normality using the Shapiro-Wilk method. It was determined that the distribution of the paper based group was not normally distributed. Accordingly, the non-parametric Mann-Whitney Test method was used to determine the statistical significance between the groups. The test showed that there was no statistical significance between the web and paper based groups.
No convincing evidence the hippocampus is associated with working memory

ABSTRACT In a previous discussion paper , twenty-six working memory fMRI studies that reported activity in the hippocampus were systematically analyzed. None of these studies provided convincing evidence that the hippocampus was active during the late delay phase, the only period in which working memory can be isolated from long-term memory processes. Based on these results, it was concluded that working memory does not activate the hippocampus. Six commentaries on the discussion paper were received from Courtney (2022), Kessels and Bergmann (2022), Peters and Reithler (2022), Rose and Chao (2022), Stern and Hasselmo (2022), and Wood et al. (2022). Based on these commentaries, the present response paper considered whether there is evidence of sustained hippocampal activity during the working memory delay period based on depth-electrode recording, whether there are activity-silent working memory mechanisms in the hippocampus, and whether there is hippocampal lesion evidence indicating this region is important for working memory. There was no convincing electrophysiological or neuropsychological evidence that the hippocampus is associated with working memory maintenance, and activity-silent mechanisms were arguably speculative. Given that only a small fraction (approximately 5%) of working memory fMRI studies have reported hippocampal activity and lesion evidence indicates the hippocampus is not necessary for working memory, the burden of proof is on proponents of the view that the hippocampus is important for working memory to provide compelling evidence to support their position. To date, from my perspective, there is no convincing evidence that the hippocampus is associated with working memory.
White Matter Hyperintensity Volume and Amyloid-PET Synergistically Impact Memory Independent of Tau-PET in Older Adults Without Dementia

Background: Alzheimer’s disease (AD) and cerebrovascular disease are common, co-existing pathologies in older adults. Whether the effects of cerebrovascular disease and AD biomarkers on cognition are additive or synergistic remains unclear. Objective: To examine whether white matter hyperintensity (WMH) volume moderates the independent association between each AD biomarker and cognition. Methods: In 586 older adults without dementia, linear regressions tested the interaction between amyloid-β (Aβ) positron emission tomography (PET) and WMH volume on cognition, independent of tau-PET. We also tested the interaction between tau-PET and WMH volume on cognition, independent of Aβ-PET. Results: Adjusting for tau-PET, the quadratic effect of WMH interacted with Aβ-PET to impact memory. There was no interaction between either the linear or quadratic effect of WMH and Aβ-PET on executive function. There was no interaction between WMH volume and tau-PET on either cognitive measure. Conclusion: Results suggest that cerebrovascular lesions act synergistically with Aβ to affect memory, independent of tau, highlighting the importance of incorporating vascular pathology into biomarker assessment of AD.
Effect of early achievement of energy target by different nutritional support strategies on nosocomial infections in patients undergoing major abdominal surgery: a secondary analysis of two randomized clinical trials

Background: The effect of early achievement of energy targets (EAETs) using different nutritional support strategies in patients undergoing major abdominal surgery is unclear. This study determined the impact of EAETs on the incidence of nosocomial infections in patients undergoing major abdominal surgery. Methods: This was a secondary analysis of two open-label randomized clinical trials. Patients from the general surgery department of 11 academic hospitals in China undergoing major abdominal surgery and at nutritional risk (Nutritional risk screening 2002≥3) were divided into two groups based on whether they met the 70% energy targets, the EAET (521 EAET and non-achievement of energy target (114 NAET) groups. The primary outcome was the incidence of nosocomial infections between postoperative day 3 and discharge, and the secondary outcomes were actual energy and protein intake, postoperative noninfectious complications, intensive care unit admission, mechanical ventilation, and hospital stay. Results: Overall, 635 patients [mean (SD) age, 59.5 (11.3) years] were included. The EAET group received more mean energy between days 3 and 7 than the NAET group (22.7±5.0 vs. 15.1±4.8 kcal/kg/d; P<0.001). The EAET group had significantly fewer nosocomial infections than the NAET group [46/521(8.8%) vs. 21/114(18.4%); risk difference, 9.6%; 95% CI, 2.1–17.1%; P=0.004]. A significant difference was found in the mean (SD) number of noninfectious complications between the EAET and NAET groups [121/521(23.2%) vs. 38/114(33.3%); risk difference, 10.1%; 95% CI, 0.7–19.5%; P=0.024]. The nutritional status of the EAET group was significantly improved at discharge compared with the NAET group (P<0.001), and other indicators were comparable between groups. Conclusion: EAETs was associated with fewer nosocomial infections and improved clinical outcomes, regardless of the nutritional support strategy (early enteral nutrition alone or combined with early supplemental parenteral nutrition).
Work in nursing homes and occupational exposure to endotoxin and bacterial and fungal species

Abstract Indoor microbial exposure may cause negative health effects. Only little is known about the occupational microbial exposure in nursing homes and the factors that influence the exposure. The exposure in nursing homes may be increased due to close contact with elderly persons who may carry infectious or antimicrobial-resistant microorganisms and due to handling of laundry, such as used clothing and bed linen. We investigated the microbial exposure in 5 nursing homes in Denmark, by use of personal bioaerosol samples from different groups of staff members taken during a typical working day, stationary bioaerosol measurements taken during various work tasks, sedimented dust samples, environmental surface swabs, and swabs from staff members’ hands. From the samples, we explored bacterial and fungal concentrations and species composition, endotoxin levels, and antimicrobial resistance in Aspergillus fumigatus isolates. Microbial concentrations from personal exposure samples differed among professions, and geometric means (GM) were 2,159 cfu/m3 (84 to 1.5 × 105) for bacteria incubated on nutrient agar, 1,745 cfu/m3 (82 to 2.0 × 104) for bacteria cultivated on a Staphylococcus selective agar, and 16 cfu/m3 air for potential pathogenic fungi incubated at 37 °C (below detection limit to 257). Bacterial exposures were elevated during bed making. On surfaces, the highest bacterial concentrations were found on bed railings. The majority of bacterial species found were related to the human skin microflora, such as different Staphylococcus and Corynebacterium species. Endotoxin levels ranged from 0.02 to 59.0 EU/m3, with a GM of 1.5 EU/m3. Of 40 tested A. fumigatus isolates, we found one multiresistant isolate, which was resistant towards both itraconazole and voriconazole, and one isolate resistant towards amphotericin B. In conclusion, we give an overview of the general microbial exposure in nursing homes and show that microbial exposures are higher for staff with more care and nursing tasks compared with administrative staff.
A hierarchical multimode molecular stress function model for linear polymer melts in extensional flows

A novel hierarchical multimode molecular stress function (HMMSF) model for linear polymer melts is proposed, which implements the basic ideas of (i) hierarchical relaxation, (ii) dynamic dilution, and (iii) interchain tube pressure. The capability of this approach is demonstrated in modeling the extensional viscosity data of monodisperse, bidisperse, and polydisperse linear polymer melts. Predictions of the HMMSF model, which are solely based on the linear-viscoelastic relaxation modulus and a single free model parameter, the segmental equilibration time, are compared to elongational viscosity data of monodisperse polystyrene melts and solutions as well as to the elongational viscosity data of a bidisperse blend of two monodisperse polystyrenes, and good agreement between model and experimental data is observed. By using a simplified relation between the Rouse stretch-relaxation times and the relaxation times of the melts, the modeling is extended to the uniaxial, equibiaxial, and planar extensional viscosity data of a high-density polyethylene, the uniaxial and equibiaxial extensional viscosity data of a polydisperse polystyrene, the elongational viscosity data of three high-density polyethylenes, and a linear low-density polyethylene. For polydisperse melts, the modeling is again based exclusively on the linear-viscoelastic relaxation modulus with only one material parameter, the dilution modulus, which quantifies the onset of dynamic dilution.