bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurement of Milk Yield in the Lactating Rat from Pup Weight and Weight Gain
Authors: Sampson David A. , Jansen G. Richard
Published: February 2024

A new method was developed that enables milk yield to be estimated from pup weight and pup weight gain in well‐nourished rats. Daily milk yield, body weight, and daily weight gain were measured over 4–5‐day periods in 38 suckling pups aged 3–13 days post‐partum. Each 24‐h period was divided into consecutive 6‐h cycles, during which dams and pups were separated for 4 h and then reunited for 2‐h suckling intervals. Daily milk yield per pup was calculated from pup weight gain during the four suckling intervals for each 24‐h period, and corrected for insensible weight loss of the pups. The following equation, relating pup milk yield to pup weight and weight gain, was obtained by stepwise forward multiple regression analysis: yield = 0.0322 + 0.0667 (weight) + 0.877 (gain); where yield is daily yield per pup (g/pup/day), weight is pup weight (g), and gain is pup weight gain per day (g/day) (n = 174; F = 552.3; p < 0.001; r2 = 0.866). Per litter milk yield can be obtained by multiplying per pup yield by litter size. Using this equation, dams fed a stock diet and nursing eight pups were estimated to have produced 29.5 ml of milk on day 10 of lactation. This value is similar to yields measured by more laborious methods. SEs of yield estimates calculated with this method represent 1–3% of predicted yield values. The new method gives useful estimates of rat milk yield during the first 2 weeks of lactation from measurements that are more easily obtained than is the case with other methods.
Blood Lipids as Related to Food Intake, Body Composition, and Cardiorespiratory Efficiency in Preschool Children
Authors: Pařízková J. , Macková E. , Macková J. , Škopková M.
Published: February 2024

A group of 3‐5‐year‐old children (n = 22) with a level of somatic development and physical fitness (modified Step test) that corresponded to a previously measured representative sample was studied. The depot fat proportion was 16.3 ± 4%, and obesity was absent. Lean body mass (LBM) was 16.1 ± 1.8 kg. As in previous studies, the fat intake was higher as compared to recommended allowances. The blood cholesterol level was 4.9 ± 0.8, high density lipoproteins (HDL) 1.2 ± 0.2, low density lipoproteins (LDL) 3.6 ± 0.8, triglycerides ?? U/L. The step test index (STI) was 92 ± 9, and the cardiac efficiency index (CEI) was 0.575 ± 0.096. The sex differences were not significant, except for body weight. Marked variability was found in all characteristics measured. There were no significant relationships among somatic development, body composition, food intake, STI, CEI, blood lipids, and CK. The LBM/10 cm height index corelated significantly with CEI, CK, and fat intake.
Modification of Somatostatin Content and Binding in Jejunum from Celiac Children
Authors: Arilla Eduardo , Hernandez Manuel , Polanco Isabel , Roca Bernardo , Prieto J. Carlos , Vazquez Carlos
Published: February 2024

The concentration of somatostatin was studied in controls as well as in plasma and jejunal mucosa from celiac children with and without jejunal villous atrophy. The binding of somatostatin to cytosolic fraction, isolated from jejunal mucosa from celiac patients and controls, was also investigated. Fasting plasma somatostatin concentrations were not significantly different among the various groups studied. However, the jejunal somatostatin content was significantly higher in the group of celiac children with subtotal villous atrophy as compared to control group and celiac children with normal villous architecture. The binding of somatostatin to cytosol of jejunal mucosa was significantly decreased in the group of celiac children with subtotal villous atrophy. The present results suggest that somatostatin may be involved in the pathophysiological processes of celiac disease.
A Micromethod for Determination of Plasma Pyridoxal Phosphate and Its Use in Assessment of Storage Stability of the Vitamer
Authors: Borschel Marlene W. , Kirksey Avanelle , Hamaker Bruce R.
Published: February 2024

A widely used macromethod employing tyrosine apodecarboxylase for measurement of pyridoxal phosphate (PLP) concentration in 0.5–1.0‐ml plasma was modified to a microscale utilizing 0.1‐ml plasma. Mean PLP levels in 12 plasma samples were 160.6 ± 32.8 pmol/ml (mean ± SD) when analyzed by the macro‐method, and were not significantly different compared to those obtained by the micromethod (158.4 ± 28.2 pmol/ ml). Results of the two methods were significantly correlated (r = +0.97, p < 0.001). Plasma PLP concentrations of 11 samples determined by the micromethod ( = 151.8 ± 30.0 pmol/ml) were similar and significantly correlated (r = +0.95, p < 0.001) to levels measured in the same samples 1–2 years earlier ( = 145.1 ± 26.2 pmol/ml). This suggests that plasma PLP content of the samples was stable for up to 2 years of storage when the micro‐method was utilized for analysis. The strong significant correlation between macro‐ and micromethods attests that the micromethod is a reliable alternative to the macromethod. The micromethod is useful in instances where only small samples of plasma are available for measurement of PLP.
Sclerema Neonatorum
Authors: Lindenberg Jeffrey A. , Milstein Jay M. , Cox Kenneth L.
Published: February 2024

We cared for four neonates with transient hyperammonemia of the newborn (THAN), all of whom exhibited sclerema during their course. Sclerema is a hardening of the subcutaneous tissues, which gives the tissue a firm, rubber‐like quality. This association has not been previously reported, and it may provide a clue to early diagnosis and intervention in THAN.
Intestinal Milk‐Bolus Obstruction in Formula‐Fed Premature Infants Given High Doses of Calcium
Authors: Koletzko Berthold , Tangermann Rudolf , von Kries Rüdiger , Stannigel Hans , Willberg Björn , Radde Ingeborg , Schmidt Eberhardt
Published: February 2024

Supplementation of milk formulae with calcium salts is recommended for low birth weight infants. We observed a serious complication of calcium administration in too high a dosage. Three premature infants (birth weight 1,080–1,900 g and gestational age 28–35 weeks) developed an obstruction of the distal ileum during the second week of life, leading to multiple bowel perforations and development of septic peritonitis in two cases. All three patients required surgical removal of a bolus blocking the intestinal lumen. Analysis of the bolus material from one infant indicated that the formation of soaps from calcium and long‐chain fatty acids had caused the obstruction. All three infants had been fed a formula for premature infants with the addition of a recently introduced commercial mineral supplement, resulting in a very high calcium concentration of the feed (40.6 mmol/ L). Simulation of syringe feeding demonstrated that even higher calcium concentrations could occur in milk portions containing sedimented calcium compounds.
Proinflammatory Cytokine Expression in Gastric Tissue From Children With Helicobacter pylori–Associated Gastritis
Authors: Guiraldes Ernesto , Duarte Ignacio , Peña Alfredo , Godoy Alex , Espinosa M. Nelly , Bravo Rubén , Larraín Francisco , Schultz Marcela , Harris Paul
Published: February 2024

Background

Helicobacter pylori infection of the gastric mucosa in humans is usually acquired early in life. The chronic inflammation that ensues involves the increased production of inflammatory cytokines. Published data on production of these mediators by gastric mucosa of H. pylori–infected children are few.

Methods

Seventy‐nine children, aged 5 to 18 years, referred for upper gastrointestinal endoscopy to four separate hospitals in Chile, were studied. The concentrations of interleukin (IL)‐1β, IL‐6, IL‐8, and tumor necrosis factor α were measured in homogenates of gastric mucosal biopsy specimens. Cytokine expression was confirmed by reverse transcription polymerase chain reaction. These data were correlated with the patients' clinical, histologic and sociodemographic status.

Results

Patient rate of colonization by H. pylori was inversely correlated with socioeconomic status (P < 0.005) and positively correlated with age (P < 0.0025). In gastric mucosa, concentrations of IL‐1β, IL‐8, and tumor necrosis factor α were all significantly higher in H. pylori–positive patients than in H. pylori–negative patients and in patients who had histologic gastritis than in those with normal gastric mucosa. In patients with peptic ulcer disease, only IL‐1β and IL‐8 concentrations were significantly elevated when compared with those of patients without ulcers. Interleukin‐6 concentrations were comparable among the different groups analyzed.

Conclusions

This study suggests that increased gastric mucosal production of the proinflammatory cytokines IL‐1β and IL‐8 is probably involved in H. pylori–associated gastric damage in children and may be crucial in determining the different clinical outcomes.
Age‐Dependent Changes in the Regulation of Cyclooxygenases in the Gastrointestinal Tract After Gram‐Negative Endotoxemia
Authors: Martinez Francisco E. , Reno Carol , Trevenen Cynthia L. , Hart David A. , Belik Jaques
Published: February 2024

Background

Cyclooxygenases (COXs) modulate prostaglandin synthesis in the gastrointestinal tract. Prostaglandins have been shown to have a cytoprotective effect on bowel mucosa in adults, but no similar data are available in neonates. Thus, the purpose of the current study was to evaluate age‐dependent changes in gastrointestinal tract COX regulation after Escherichia coli lipopolysaccharide exposure in rats.

Methods

Stomach, small bowel, and large bowel COX‐1 and COX‐2 mRNA levels (reverse transcription polymerase chain reaction technique) and protein content (Western blot) were obtained from neonates (younger than 3 days old) and adult rats 18 hours after exposure to E. coli O111:B4 lipopolysaccharide toxin. Untreated animals served as controls.

Results

Stomach, small bowel, and large bowel tissue COX‐1 mRNA levels in the newborn were significantly lower (P < 0.01) than in the adult. No age‐dependent differences were found for COX‐2 mRNA levels. After lipopolysaccharide exposure, no significant changes in COX‐1 levels were seen at either age, whereas COX‐2 mRNA levels were increased only in the stomach for both ages. Western blot analysis of small bowel tissue for COX‐1 and COX‐2 showed no lipopolysaccharide‐induced changes in protein content, but the COX‐1 content was significantly lower in the newborn (P < 0.01).

Conclusions

In the rat, COX expression in the gastrointestinal tract is regulated in an age‐dependent fashion. Lower COX‐1 expression and a lack of observable increase in COX‐2 mRNA levels in the newborn small bowel after endotoxemia may render the bowel more susceptible to bowel injury early in life.
Eosinophilic Esophagitis in Children: Symptoms, Histology and pH Probe Results
Authors: Sant'Anna A. M. G. A. , Rolland S. , Fournet J. C. , Yazbeck S. , Drouin E.
Published: February 2024

Aim:

To review the authors’ experience with eosinophilic esophagitis.

Methods:

Between 1993 and 2001, the authors identified 12 patients with eosinophilic esophagitis defined on histologic criteria (≥20 eosinophils per high‐power field in the distal esophageal epithelium). The authors reviewed medical records for details of clinical presentation; laboratory data; radiologic, endoscopic, and histologic findings; and the results of continuous esophageal pH probe monitoring.

Results:

Seventy‐five percent of the patients were male. The median age at presentation was 10.8 years (range, 1–17 years). Commonly reported symptoms were dysphagia with solid food (66%), epigastric pain (42%), food impaction (50%), and vomiting (8%). Food allergy was reported in 50% and asthma in 33%. Peripheral eosinophilia (>700/mm3) was found in 42%. Upper gastrointestinal series performed in eight patients, showed esophageal luminal narrowing in three. Computed tomography, performed in two patients, revealed thickening of the esophageal wall. Esophageal pH probe monitoring, performed in nine patients, revealed no abnormal acid reflux. All of the monitored patients had episodic alkalinization of the esophagus. Upper endoscopic analysis revealed white specks on the esophageal mucosa in 42%, esophageal narrowing in 33%, esophageal rings in 25%, and esophageal furrowing in 8%. The mean eosinophils per high‐power field was 65 (range, 20–200). Histologic characteristics included juxtaluminar (33%) and peripapillary clusters of eosinophils (33%), increased papillary height (50%), and basal cell hyperplasia (34%).

Conclusion:

Solid food dysphagia was the most common feature of eosinophilic esophagitis in our patients. Alkalinization of the esophagus was found in all nine pH probe recordings of eosinophilic esophagitis patients and may represent a previously unreported characteristic of the condition.
Severe Gastroesophageal Reflux Disease and Cow Milk Hypersensitivity in Infants and Children: Disease Association and Evaluation of a New Challenge Procedure
Authors: Nielsen R. G. , Bindslev‐Jensen C. , Kruse‐Andersen S. , Husby S.
Published: February 2024

Background:

Gastroesophageal reflux disease (GERD) and cow milk hypersensitivity are frequent disorders of infancy. A possible causative association between these two entities has been suggested.

Objective:

The primary aim was to elucidate whether a causative relationship between the two entities could be established in a population of infants and children. A secondary aim was to evaluate whether cow milk challenge during esophageal pH monitoring is useful as an objective method to identify this subgroup of patients.

Methods:

Upper endoscopy followed by a 48‐hour esophageal pH monitoring with cow's milk elimination diet at day 1 and challenge at day 2. Cow milk hypersensitivity was later verified by elimination diet and a second open (in patients <3 years of age) or double‐blind placebo‐controlled (in patients ≥3 years of age) challenge. Skin prick test, specific serum immunoglobulin E and skin patch test were used as supplementary procedures. Follow‐up endoscopy and pH monitoring were performed after 3 months of treatment (omeprazole versus elimination diet dependent on evidence of food hypersensitivity).

Results:

Eighteen of 42 investigated patients had severe GERD, defined as endoscopic esophagitis and/or a reflux index >10%. Among these patients, a group of 10 patients with GERD and cow milk hypersensitivity was identified. This group had a significantly higher reflux index compared with children with primary GERD. No significant increase was noted in reflux index during simultaneous pH monitoring and milk challenge.

Conclusions:

An association between GERD and cow milk hypersensitivity was observed in both infants and children with severe GERD. Simultaneous cow milk challenge and pH monitoring had limited value as a method to identify this subgroup.
Chronic Hepatitis B Infection: Long Term Comparison of Children Receiving Interferon Alpha and Untreated Controls
Authors: Vo Thi Diem Hanh , Bourgois Annick , Bontems Patrick , Goyens Philippe , Buts Jean Paul , Nackers Fabienne , Tonglet René , Sokal Etienne Marc
Published: February 2024

Objectives:

To investigate the virological outcome of chronic hepatitis B (CH‐B) in children who received interferon alpha (IFN) compared with no treatment.

Methods:

Seventy‐four children with CH‐B (median age, 6.1 years; 44 boys) selected from a cohort of 158 cases were included and divided into two groups: IFN‐treated (n = 37) and control (n = 37). The controls were matched with the treated children by baseline alanine aminotransferase (ALT) levels, sex and age. The Kaplan‐Meier method was performed to estimate the time to clearance of hepatitis B e antigen (HbeAg) and hepatitis B surface antigen (HbsAg).

Results:

Mean duration of follow‐up was comparable in two groups (5.2 ± 3.8 years in treatment group versus 5.2 ± 3.7 years in control group, NS). HBeAg and HBsAg loss occurred in 20 (54.1%) and three treated children versus 13 (35.1%) and one untreated children (NS), respectively. The 7‐year cumulative HBeAg and HBsAg clearance rates were 47.5% and 8.9% after the first visit in the treatment group versus 33.5% and 4.0% in untreated children (NS), respectively. Elevated baseline ALT (two times upper limit of normal) had a significant effect on the long‐term cumulative rate of HBeAg seroconversion in treated patients (P = 0.01) but not in the untreated group.

Conclusions:

These findings show that the overall long‐term virological outcome does not differ significantly between IFN‐treated and untreated children but that a significant benefit of treatment on the long term rate of HBeAg seroconversion is obtained in children with higher baseline ALT levels.
Comparing instructor‐led, video‐model, and no‐instruction control tutorials for creating single‐subject graphs in Microsoft Excel: A systematic replication and extension
Authors: Zonneveld Kimberley L. M. , Cox Alison D. , Asaro Madeline M. , Hranchuk Kieva S. , Alami Arezu , Kelly Laura D. , Frijters Jan C.
Published: February 2024

Visual inspection of single‐subject data is the primary method for behavior analysts to interpret the effect of an independent variable on a dependent variable; however, there is no consensus on the most suitable method for teaching graph construction for single‐subject designs. We systematically replicated and extended Tyner and Fienup (2015) using a repeated‐measures between‐subjects design to compare the effects of instructor‐led, video‐model, and no‐instruction control tutorials on the graphing performance of 81 master's students with some reported Microsoft Excel experience. Our mixed‐design analysis revealed a statistically significant main effect of pretest, tutorial, and posttest submissions for each tutorial group and a nonsignificant main effect of tutorial group. Tutorial group significantly interacted with submissions, suggesting that both instructor‐led and video‐model tutorials may be superior to providing graduate students with a written list of graphing conventions (i.e., control condition). Finally, training influenced performance on an untrained graph type (multielement) for all tutorial groups.
Novel cyano functional small molecule photosensitizers with amplified electron injection and photovoltaic attributes: molecular modelling towards efficient dye‐sensitized solar cells
Authors: Nadeem Sehar , Khan Muhammad Usman , Hussain Riaz , Shafiq Faiza , Alhokbany Norah
Published: February 2024

BACKGROUND

The exploration of novel photosensitizers with reverberant optoelectronic features for dye‐sensitized solar cells (DSSCs) is a frontline area of research. In this respect, attempts have been made to design a series of novel organic dyes (JFK‐1–JFK‐10) with D‐π‐A framework by π‐spacer modification strategy. The suitability of developed sensitizers for DSSCs applications is confirmed by executing natural bond orbital (NBO) analysis, transition density matrix (TDM) analysis, frontier molecular orbital (FMO) analysis, density of state (DOS) analysis, binding energy (Eb), electron regeneration energy (ΔGreg), free energy of injection (ΔGinject), electronic coupling constant (VRP), and intramolecular charge transfer (ICT) parameters qCT (e‐), DCT (Å), H index (Å), ∆(Å), t index (Å), μCT (D).

RESULTS

The calculated results of these analyses show that replacing the thiophene (B0) π‐spacer with extended conjugated thiazole and thiophene as a π‐spacer (B1‐B10) results in significantly lowered FMO energy levels, broader λmax values, and ICT parameters respectively. All the proposed dyes could be used as excellent sensitizers for DSSCs; the B9 spacer in JFK‐9 makes JFK‐9 a highly efficient candidate for the high‐efficiency of DSSCs due to promising photovoltaic characteristics, like the reduced Egap (4.386 eV), longer λmax(427.989 nm), longer excited state lifetimes (1.483 ns), a lower ΔGreg (1.807 eV), a greater dipole moment of (9.475 D), and large qCT (0.546), LHE (0.981), and eVOC (1.729 eV).

CONCLUSION

The fabricated dyes’ (F1‐F9) photoelectronic and chemical transfer parameters near the titania‐electrolyte interface (dyes@TiO2) proved have better accumulation and recombination of dyes@TiO2 model. The adsorption energies calculated of all compounds provide a deep insight into adsorption and charge transfer to a semiconductor TiO2 conduction band. Hence, these modeled dyes (JFK‐1‐JFK‐10) could be used as efficient DSSCs and open new avenues for researchers to synthesize high‐performance DSSCs. © 2024 Society of Chemical Industry (SCI).
An assessment of preclinical removable prosthodontics based on multiple‐choice questions: Stakeholders' perceptions
Authors: Shammas Mohammed , Nagda Suhasini , Shah Chinmay , Baxi Gaurang , Gadde Praveen , Sachdeva Shabina , Gupta Deeksha , Wali Othman , Dhall Rupinder Singh , Gajdhar Shaiq
Published: February 2024

Purpose

Item analysis of multiple‐choice questions (MCQs) is an essential tool for identifying items that can be stored, revised, or discarded to build a quality MCQ bank. This study analyzed MCQs based on item analysis to develop a pool of valid and reliable items and investigate stakeholders’ perceptions regarding MCQs in a written summative assessment (WSA) based on this item analysis.

Methods

In this descriptive study, 55 questions each from 2016 to 2019 of WSA in preclinical removable prosthodontics for fourth‐year undergraduate dentistry students were analyzed for item analysis. Items were categorized according to their difficulty index (DIF I) and discrimination index (DI). Students (2021–2022) were assessed using this question bank. Students’ perceptions of and feedback from faculty members concerning this assessment were collected using a questionnaire with a five‐point Likert scale.

Results

Of 220 items when both indices (DIF I and DI) were combined, 144 (65.5%) were retained in the question bank, 66 (30%) required revision before incorporation into the question bank, and only 10 (4.5%) were discarded. The mean DIF I and DI values were 69% (standard deviation [Std.Dev] = 19) and 0.22 (Std.Dev = 0.16), respectively, for 220 MCQs. The mean scores from the questionnaire for students and feedback from faculty members ranged from 3.50 to 4.04 and from 4 to 5, respectively, indicating that stakeholders tended to agree and strongly agree, respectively, with the proposed statements.

Conclusion

This study assisted the prosthodontics department in creating a set of prevalidated questions with known difficulty and discrimination capacity.
Using varied technological agents‐assisted simultaneous prompting for teaching discrete skills to children with developmental disabilities
Authors: Kirsal Ayten Ozkirac , Kahveci Gul
Published: February 2024

This study examines the effectiveness of combining simultaneous prompting method with small group teaching through computer projection, SMART board, tablet computer and humanoid robot to teach discrete skills to children with developmental disabilities (CDD). The study included 14 CDD aged 10–15. It utilizes a multiple probe design across behaviors and probe conditions and replicates them across subjects. Each participant is taught discrete skills within a small group teaching arrangement. The study includes daily probes, full probes, teaching sessions, generalization, and follow‐up sessions. It also collects interobserver reliability and application reliability data. Graphical analysis demonstrates the effectiveness of computer‐based simultaneous prompting incorporating different technologies in a small group teaching setting. Additionally, we examined differences in children's responses to different technological agents in teaching discrete skills to children with developmental disabilities. The study provided preliminary data on which of these agents is best. The results demonstrate its effectiveness by showing that participants maintained the learned behaviors and applied them to a variety of tools, equipment, and individuals in the first, third, and fourth weeks after the intervention. Additionally, the study highlights the subjects' high accuracy in acquiring behavior through observational learning. Finally, simple humanoid robots, tablets, smart SMART boards, and computer projections have been effective in teaching discrete skills to CDD, respectively.
Surface characteristics of additively manufactured CoCr and Ti6Al4V dental alloys: The effects of carbon and gold thin film coatings, and alkali‐heat treatment
Authors: Yilmaz Bengi , Ayyildiz Simel , Kalyoncuoglu Ulku Tugba , Tahmasebifar Aydin , Baran Erkan Türker
Published: February 2024

This study investigates the impact of surface modifications on additively manufactured CoCr and Ti6Al4V dental alloys, focusing on surface properties. Thin film carbon (C) and gold (Au) coatings, as well as alkali‐heat treatment, were applied to the high‐ and low‐polished specimens. Scanning electron microscopy (SEM) showed that thin film coatings retained the underlying surface topography, while the alkali‐heat treatment induced distinct morphological changes. Energy‐dispersive x‐ray spectroscopy (EDS) analysis revealed that C‐coating enriched surfaces with C, and Au‐coating introduced detectable amounts of Au. Nevertheless, signs of coating delamination were observed in the high‐polished specimens. Alkali‐heat treatment led to the formation of a sodium titanate layer on Ti6Al4V surfaces, confirmed by sodium presence and Fourier transform infrared spectroscopy (FTIR) results showing carbonate bands. Surface roughness measurements with atomic force microscopy (AFM) showed that C‐coating increased surface roughness in both high‐ and low‐polished alloys. Au‐coating slightly increased roughness, except for low‐polished Au‐coated Ti6Al4V, where a decrease in roughness was observed compared to low‐polished bare Ti6Al4V, likely due to surface defects present in the latter resulting from the additive manufacturing process. Alkali‐heat treatment led to a pronounced increase in roughness for both alloys, particularly for Ti6Al4V. Both thin film coatings decreased the water contact angles in all specimens in varying magnitudes, indicating an increase in wettability. However, the alkali‐heat treatment caused a substantial decrease in contact angles, resulting in a highly hydrophilic state for Ti6Al4V. These findings underscore the substantial impact of surface modifications on additively manufactured dental alloys, potentially influencing their clinical performance.

Research Highlights

Thin film coatings and chemical/heat treatment modify the surface properties of additively manufactured dental alloys.

The surfaces of the alloys get rougher and more hydrophilic after alkali‐heat treatment.

Thin gold coatings exhibit potential adhesion challenges.
Intra and interspecific differences in desiccation tolerance in native and alien Antarctic springtails in geothermal grounds
Authors: Escribano‐Álvarez Pablo , Castro Mario G. , Pertierra Luis R. , Olalla‐Tárraga Miguel Á.
Published: February 2024

The extreme low humidity and temperatures in Antarctica make it one of the harsher areas for life on our planet. In a global change context, environmental barriers that prevented the arrival of alien species in Antarctica are weakening. Deception Island, one of the four active volcanoes of Antarctica, is especially vulnerable to the impacts of alien species. Geothermal areas (GA) in this Island offer unique microclimatic conditions that could differentially affect native and alien soil arthropods. Here we explore the desiccation tolerance of a native (Cryptopygus antarcticus) and an alien (Proisotoma minuta) springtail (Collembola) species to these extreme environmental conditions. GA and non‐geothermal areas (NGA) were selected to evaluate intra‐ and interspecific variation in desiccation tolerance. Populations of P. minuta from GA had greater desiccation tolerance than populations from NGA. However, desiccation tolerance of C. antarcticus did not differ between GA and NGA. This native species had greater desiccation tolerance than the alien P. minuta, but also greater body size. Our findings show that the alien P. minuta responds differently to environmental conditions than the native C. antarcticus. Furthermore, body size may influence desiccation tolerance in these two springtail species.
BIPOC students' paths to genetic counseling: Results from a longitudinal qualitative study
Authors: Carmichael Nikkola , Zayhowski Kimberly , Diaz Joselyn Saenz
Published: February 2024

Despite diversity initiatives, the genetic counseling profession continues to exhibit limited racial and ethnic diversity, with relatively stagnant representation of Black, Indigenous, and People of Color (BIPOC) individuals. Prior research has found that BIPOC high school and college students are less likely to be aware of genetic counseling and learn about it later than their white peers. Financial barriers and familial discouragement based on a preference for medical school may disproportionately impact BIPOC applicants. Here, we report the first set of results from a longitudinal constructivist grounded theory study exploring the training experiences of BIPOC genetic counseling students. Through reflexive thematic analysis of semi‐structured interviews conducted with 26 first‐year BIPOC genetic counseling students, we identified five themes pertaining to participants' paths to enrolling in a genetic counseling program: (1) Deciding to pursue genetic counseling, (2) Family's reaction to genetic counseling, (3) Deciding where to submit applications, (4) Barriers during admissions, and (5) Ranking programs. Participants discovered genetic counseling later in their academic journey, often necessitating gap years to complete admissions requirements. Limited guidance from advisors was commonly cited as a barrier by first‐generation college students. Family support seems to be a key factor in participants' successful pursuit of genetic counseling, but participants described challenges explaining the career, particularly to parents who did not speak English. In addition, some participants encountered resistance about changing prior plans to go to medical school. Finally, while participants prioritized cost and location in their initial decision about where to submit applications, their ranking of programs was heavily influenced by experiences during interviews, where they favored conversational interviews and evaluated if they would “fit in” at the program. These findings underscore the need for proactive measures, such as early exposure initiatives, mentorship programs, and resources to facilitate family support, to promote diversity in genetic counseling.
New quinoxaline‐piperazine‐oxazole conjugates: Synthesis, in vitro anticancer, in silico ADMET, and molecular docking studies
Authors: Ferazoddin Mohammad , Marupati Siddhartha , Dasari Gouthami , Syeda Arshiya Banu , Ali Mohammad Imtiyaz , Manchal Ravinder , Bokkala Karthik , Bandari Srinivas
Published: February 2024

In this paper, we describe the synthesis of some new quinoxaline‐piperazine‐oxazole amide conjugates 6a‐n from 3‐chloroquinoxaline‐2‐carbonitrile using well‐known reaction sequences. The synthesized compounds were characterized by 1H NMR,13C NMR, and mass spectral analysis. The compounds were tested for their in vitro antiproliferative activity toward four different cancer cell lines such as PC‐3, MCF‐7, DU‐145, and A‐549 by MTT method. The compounds, 6c, 6h, 6i, and 6n were found to be more potent than the standard Erlotinib. In vitro tyrosine kinase EGFR inhibition studies using four potent compounds revealed that 6n has double inhibiting tendency with value IC50 of 0.22 μM and 6h with value of IC50 0.27 μM compared to reference compound. Molecular docking studies of active compounds, 6c, 6h, 6i, and 6n on EGFR receptor suggested that all the compounds have more binding energies than that of Erlotinib. Furthermore, the in silico pharmacokinetic profile was accomplished for the active compounds, 6c, 6h, 6i, and 6n using SWISS/ADME and pk CSM, whereas compounds, 6h, 6i, and 6c followed Lipinski rule, Veber rule, Egan rule and Muegge rule. The remaining compound 6n did not follow Lipinski rule, Ghose rule because one common violation, that is, because of high molecular weight (MW > 350).
Dynamics of serum cross‐neutralization capacity against SARS‐CoV‐2 Delta variant in convalescent COVID‐19 patients
Authors: Nedelcu Iulia , Florian Paula , Daniel Ion George Nicolae , Militaru Eliza , Damalan Anca , Popescu Costin‐Ioan , Hristea Adriana
Published: February 2024

The magnitude and breadth of the neutralizing antibody response against variants of concern following natural infection would provide valuable insights regarding the immune response induced by severe acute respiratory syndrome‐related coronavirus (SARS‐CoV‐2) infection. Herein, 25 patients were followed at 30 ±7 (Visit 1), 90± 15 (Visit 2), and 180 ± 15 (Visit 3) days post symptom onset (PSO). The neutralization titers against both Wuhan‐Hu‐1 (WT) and Delta variant were analyzed in parallel along with anti‐Spike antibodies (anti‐S1/S2 immunoglobulin G [IgG]). The median values of half‐maximal neutralization titer (NT50) for the WT and Delta variants decreased by 75.8% and 82.2% at Visit 2 and by 85.4% and 81.4% at Visit 3, respectively. At Visit 1, the correlation between the anti‐S1/S2 IgG and Nabs titers for the Delta variant was moderate for WT (r = 0.58) and weak for the Delta variant (r = 0.39). However, the correlation coefficient consistently remained above 0.7, with a very strong correlation at Visit 3 for both WT and Delta variants (r = 0.81). The dynamics of anti‐S1/S2 IgG antibodies, NT50, and cross‐neutralization index correlated at different time points PSO. Longitudinal analysis of the cross‐neutralization capacity of immune sera will inform upon the durability of the immune response against SARS CoV‐2 variants.
Landscape of T cell epitopes displays hot mutations of SARS‐CoV‐2 variant spikes evading cellular immunity
Authors: Gan Mengze , Cao Jinge , Zhang Yandi , Fu Hui , Lin Xiaosong , Ouyang Qi , Xu Xinyue , Yuan Yin , Fan Xionglin
Published: February 2024

The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has been accompanied by the emergence of viral mutations that pose a great challenge to existing vaccine strategies. It is not fully understood with regard to the role of mutations on the SARS‐CoV‐2 spike protein from emerging viral variants in T cell immunity. In the current study, recombinant eukaryotic plasmids were constructed as DNA vaccines to express the spike protein from multiple SARS‐CoV‐2 strains. These DNA vaccines were used to immunize BALB/c mice, and cross‐T cell responses to the spike protein from these viral strains were quantitated using interferon‐γ (IFN‐γ) Elispot. Peptides covering the full‐length spike protein from different viral strains were used to detect epitope‐specific IFN‐γ+ CD4+ and CD8+ T cell responses by fluorescence‐activated cell sorting. SARS‐CoV‐2 Delta and Omicron BA.1 strains were found to have broad T cell cross‐reactivity, followed by the Beta strain. The landscapes of T cell epitopes on the spike protein demonstrated that at least 30 mutations emerging from Alpha to Omicron BA.5 can mediate the escape of T cell immunity. Omicron and its sublineages have 19 out of these 30 mutations, most of which are new, and a few are inherited from ancient circulating variants of concerns. The cross‐T cell immunity between SARS‐CoV‐2 prototype strain and Omicron strains can be attributed to the T cell epitopes located in the N‐terminal domain (181–246 aa [amino acids], 271–318 aa) and C‐terminal domain (1171–1273 aa) of the spike protein. These findings provide in vivo evidence for optimizing vaccine manufacturing and immunization strategies for current or future viral variants.
Characteristics, clinical laboratory, histopathology, and outcomes of glycogenic hepatopathy in children
Authors: Jarasvaraparn Chaowapong , González Iván A. , Tolliver Kyla M. , Haddad Nadine G. , Molleston Jean P.
Published: February 2024

Introduction

Glycogenic hepatopathy (GH) is a rare complication of type I diabetes mellitus (DM1), resulting in abnormal deposition of glycogen in the liver due to poor glycemic control. Clinical characteristics and natural history of GH are not completely understood in children. In this study, we investigated clinical, biochemical, histologic parameters and outcomes in children with GH.

Method

This was a retrospective review of patients less than 18 years old diagnosed with GH and DM. GH was confirmed on liver biopsy. Medical records were reviewed for clinical presentation, laboratory tests, and clinical outcomes. Liver biopsy findings were reviewed by a pediatric pathologist (I. A. G.).

Results

Nine children were diagnosed with GH and type 1 DM. The median age at diagnosis of GH was 16 (IQR 14.5−17) years. Duration of diagnosis of DM until GH diagnosis was 7 (IQR 5−11) years. The median frequency of diabetic ketoacidosis before GH diagnosis was three times (IQR 2−5.25). Peak Aspartate transaminase (AST) and Alanine transaminase (ALT) ranged from 115 to 797, and 83−389 units/L, respectively. Only two children had mild fibrosis. Seven of nine had steatosis without steatohepatitis. There was no correlation between glycosylated hemoglobin (HbA1c), or other laboratory tests and liver fibrosis on biopsy. HbA1c was 11.2 (IQR 10.2−12.8) at GH diagnosis and 9.8 (IQR 9.5−10.8) with normalization of liver enzymes.

Conclusion

GH appears to be related to poor glycemic control in teenagers with long‐term diabetes. GH presents with high to very high aminotransferase especially AST > ALT and resolves with modestly improved glycemic control. Diffuse hepatocyte swelling, steatosis, minimal fibrosis without hepatocyte ballooning or lobular inflammation are most common histological features.
Bone diseases in a Pleistocene South American native ungulate species: the case of Toxodon platensis Owen, 1837 (Mammalia, Notoungulata, Toxodontidae)
Authors: Luna Carlos A. , De S. Barbosa Fernando H. , Gonzalez Romina , Miño‐Boilini Ángel R. , Repetto Carolina , Zurita Alfredo E.
Published: February 2024

Knowledge of bone pathologies in South American native ungulates is very scarce, which contrasts with other groups of megamammals such as xenarthrans and proboscideans. In this paper, based on morphological and histological analysis, we describe different bone pathologies in two specimens of Toxodon platensis Owen (Notoungulata), one of the most common taxa in the Late Pleistocene faunistic associations of northeastern Argentina. Subchondral erosions on the metacarpus and magnum, non‐marginal syndesmophytes and enthesitis on the vertebral body, the neural column and the zygapophyseal joint of the lumbar vertebrae, as well as a particular periosteal reaction on the ribs, have been interpreted as manifestations of spondyloarthropathies in one of the analyzed individuals. In the same individual, a process of fusion and bone neoformation is observed in the caudal vertebrae, which seems to correspond both to the aforementioned spondyloarthropathy and to an infectious process. A lesion on the fourth metatarsus of a second individual with an evident cloaca is suggestive of osteomyelitis; this is the first report of this pathology in notoungulates. It seems possible that some of these pathologies may have been facilitated by factors such as body mass, mode of locomotion and/or environment. These findings provide insight into some aspects of the ecology of this particular group of extinct South American megamammals.
High‐Sensitive and Background‐Free Coherent Anti‐Stokes Raman Scattering Microscopy Using Delay Modulation
Authors: Wu Fan , Li Shangyu , Chen Xun , Yue Shuhua , Hong Weili , Wang Pu
Published: February 2024

Coherent anti‐Stokes Raman scattering (CARS) microscopy has demonstrated a powerful platform for label‐free, non‐invasive, and chemically specific imaging of biological samples. However, the non‐resonant background limits its ability to detect weak Raman signals. Here, an approach to eliminate the non‐resonant background in CARS using delay modulation (DM) is presented, which is enabled by an acousto‐optic modulator and spectral focusing. The results demonstrate that DM‐CARS reduces the non‐resonant background by 10 times and improves detection sensitivity by 100‐fold over normal CARS. It also shows that DM‐CARS has potential applications in tracking heavy water metabolism in bacteria for antimicrobial susceptibility testing and imaging liver tumor tissues. Furthermore, a handheld DM‐CARS device has also demonstrated for in vivo imaging, which can be beneficial in various applications.
Multichannel Linear and Nonlinear Information Encryptions with Malus Metasurfaces
Authors: Sun Yuexin , Geng Guangzhou , Wang Yanchun , Zhang Yuebian , Li Zhancheng , Liu Wenwei , Cheng Hua , Chen Shuqi
Published: February 2024

The superior capability of wavefront manipulation makes metasurfaces a promising platform for implementing high‐density information storage and multifold optical encryption. Although some metasurfaces have realized information encryption, it is still challenging to implement polarization‐encrypted grayscale images in both linear and nonlinear channels. Here, a novel approach to realize multichannel linear and nonlinear information encryptions is proposed based on nonlinear Malus metasurfaces composed of single‐sized meta‐atoms, in which the polarization states of the linear and nonlinear signals can be decoupled. As a proof of concept, two distinct grayscale images with different polarizations have been encrypted in the fundamental and second harmonic wave channels simultaneously. Besides, by further introducing the nonlinear Pancharatnam‐Berry phase, a tri‐channel polarization encrypted metasurface with a multi‐level grayscale image in the near field and two holographic images in the far field has been experimentally demonstrated at the second harmonic frequency. This work provides more degrees of freedom for multichannel information storage and opens an avenue for optical information encryption in both linear and nonlinear regimes.
Motor and Non‐motor Outcomes of Deep Brain Stimulation across the Genetic Panorama of Parkinson's Disease: A Multi‐Scale Meta‐Analysis
Authors: Asimakidou Evridiki , Xiromerisiou Georgia , Sidiropoulos Christos
Published: February 2024

Background

In the era of modern medicine, where high‐throughput sequencing techniques are readily available, it is desirable to elucidate the role of genetic background in patients with Parkinson's Disease (PD) undergoing Deep Brain Stimulation (DBS). Genetic stratification of PD patients undergoing DBS may assist in patient selection and prediction of clinical outcomes and complement existing selection procedures such as levodopa challenge testing.

Objective

To capture a broad spectrum of motor and non‐motor DBS outcomes in genetic PD patients with data from the recently updated literature.

Methods

A multi‐scale meta‐analysis with 380 genetic PD cases was conducted using the Cochrane Review Manager, JASP software and R.

Results

This meta‐analysis revealed that overall, patients with genetic PD are good candidates for DBS but the outcomes might differ depending on the presence of specific mutations. PRKN carriers benefited the most regarding motor function, daily dose medication and motor complications. However, GBA carriers appeared to be more prone to cognitive decline after subthalamic nucleus DBS accompanied by a low quality of life with variable severity depending on genetic variants and concomitant alterations in other genes. Apart from GBA, cognitive worsening was also observed in SNCA carriers. Pre‐operative levodopa responsiveness and a younger age of onset are associated with a favorable motor outcome.

Conclusion

A personalized approach with a variant‐based risk stratification within the emerging field of surgicogenomics is needed. Integration of polygenic risk scores in clinical‐decision making should be encouraged.
Renegotiations after procurement auctions: Coping with supply disruptions due to underestimating costs
Authors: Cai Dong , Guo Chunxiang , Lai Kee‐hung
Published: February 2024

It is common for suppliers to underestimate costs in procurement auctions, thereby decreasing the bid price and profit on completion of the supply, and potentially resulting in supply disruptions. We study the bidding decisions of suppliers that underestimate costs when the buyer uses first‐price or second‐price sealed‐bid procurement auctions. We study the effects of underestimating costs on the bid prices and performance decisions under different auction modes and propose renegotiations after procurement auctions to cope with supply disruptions. The results show that: (1) using first‐price or second‐price auctions, underestimating costs does not guarantee a positive profit on completion of the supply. When the winning supplier's degree of underestimation is high enough, underestimating costs may cause supply disruptions. (2) When the buyer faces supply disruptions, if the expected payment for re‐selecting another supplier is not less than a certain threshold value, the buyer can prevent supply disruptions through renegotiations after procurement auctions. (3) Compared to the situation where all suppliers' budgeted costs are accurate, underestimating costs always decreases the supplier's profit. For the buyer, when the supplier completes the supply under the original or renegotiated contract, underestimating costs can decrease the procurement costs. Finally, we show the main conclusions with numerical examples.
Development and therapeutic potential of GSPT1 molecular glue degraders: A medicinal chemistry perspective
Authors: Chang Xiujin , Qu Fangui , Li Chunxiao , Zhang Jingtian , Zhang Yanqing , Xie Yuanyuan , Fan Zhongpeng , Bian Jinlei , Wang Jubo , Li Zhiyu , Xu Xi
Published: February 2024

Unprecedented therapeutic targeting of previously undruggable proteins has now been achieved by molecular‐glue‐mediated proximity‐induced degradation. As a small GTPase, G1 to S phase transition 1 (GSPT1) interacts with eRF1, the translation termination factor, to facilitate the process of translation termination. Studied demonstrated that GSPT1 plays a vital role in the acute myeloid leukemia (AML) and MYC‐driven lung cancer. Thus, molecular glue (MG) degraders targeting GSPT1 is a novel and promising approach for treating AML and MYC‐driven cancers. In this Perspective, we briefly summarize the structural and functional aspects of GSPT1, highlighting the latest advances and challenges in MG degraders, as well as some representative patents. The structure‐activity relationships, mechanism of action and pharmacokinetic features of MG degraders are emphasized to provide a comprehensive compendium on the rational design of GSPT1 MG degraders. We hope to provide an updated overview, and design guide for strategies targeting GSPT1 for the treatment of cancer.
Stochastic COVID‐19 epidemic model incorporating asymptomatic and isolated compartments
Authors: Caraballo Tomás , Bouzalmat Ibrahim , Settati Adel , Lahrouz Aadil , Brahim Abdeladim Nait , Harchaoui Bilal
Published: February 2024

This study delves into the intricate dynamics of the COVID‐19 epidemic by extending a deterministic compartmental model incorporating asymptomatic, quarantined and isolated compartments, with a stochastic model capturing the natural randomness of the processes. Traditional analytical methods face challenges in capturing the complexities arising from the dynamical interactions between these compartments. Our primary goal is to unravel the long‐term behavior and stability of the COVID‐19 epidemic model using this innovative stochastic framework. In this work, we establish stochastic threshold conditions that govern disease extinction and persistence while exploring the characteristics of a stationary distribution. The derived insights, anchored in rigorous theoretical underpinnings, are further substantiated through an exhaustive numerical analysis. Crucially, the parameters of our model are meticulously calibrated against empirical data pertaining to the COVID‐19 outbreak in India. By bridging theory and practical applications, we showcase the significance of stochastic modeling in comprehending the intricate nature of epidemic dynamics, specifically within the context of COVID‐19.