bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensitivity analysis and application to trotting of a noninvasive method to calculate flexor tendon forces in the equine forelimb
Authors: Meershoek Liduin S. , Lanovaz Joel L.
Published: December 2005

Objective—To test the sensitivity to measurement and modeling errors of a method for noninvasive calculation of flexor tendon forces in the equine forelimb and to calculate tendon forces for Dutch Warmblood horses during trotting.

Sample Population—A normative set of kinematic and ground-reaction force (GRF) data obtained from horses during trotting in another study.

Procedure—Forces in the flexor tendons were calculated from the data set before and after addition of fixed relative and absolute errors. Amount of error was based on normal accuracy of the variables. A similar analysis was performed for a measure of strain of the accessory ligament of the deep digital flexor tendon.

Results—The only errors that had a substantial influence on accuracy were modeling errors in the mechanical properties of the suspensory ligament and measurement errors in the point of application of the GRF and position of the marker on the distal interphalangeal joint. Influence of the measurement errors could be minimized by applying usual correction methods.

Conclusion and Clinical Relevance—After correction of measurement errors, the method can be used to calculate mean tendon forces for a group of horses and to evaluate the influence of factors such as surface properties, type of shoe, speed, and fatigue on tendon forces. The method could become an important tool for use in research on the cause, prevention, and treatment of tendon injuries in horses. (Am J Vet Res2001;62:1594–1598)
Number of Cryptosporidium parvum oocysts or Giardia spp cysts shed by dairy calves after natural infection
Authors: Nydam Daryl V. , Wade Susan E. , Schaaf Stephanie L. , Mohammed Hussni O.
Published: December 2005

Objective—To determine the total number ofCryptosporidium parvumoocysts andGiardiaspp cysts shed by dairy calves during the period when they are most at risk after natural infection.

Animals—478 calves naturally infected withC parvumand 1,016 calves naturally infected withGiardiaspp.

Procedure—Oocysts or cysts were enumerated from fecal specimens. Distribution of number of oocysts or cysts versus age was used to determine the best fitting mathematic function. Number of oocysts or cysts per gram of feces for a given duration of shedding was computed by determining the area under the curve. Total number of oocysts or cysts was calculated by taking the product of the resultant and the expected mass of feces.

Results—Intensity ofC parvumoocyst shedding was best described by a second-order polynomial function. Shedding increased from 4 days of age, peaked at day 12, and then decreased. An infected 6-day-old calf would produce 3.89 X 1010oocysts until 12 days old. Pattern of shedding ofGiardiaspp cysts was best described by exponential functions. Intensity of shedding increased from 4 days of age, peaked at day 14, and then decreased. An infected calf would produce 3.8 X 107cysts from day 50 until day 56.

Conclusion and Clinical Relevance—The large number of oocysts and cysts shed indicates that shedding by dairy cattle poses a risk for susceptible calves and people. Estimates reported here may be useful to aid in designing cost-effective strategies to manage this risk. (Am J Vet Res2001;62:1612–1615)
Development of a functional scoring system in dogs with acute spinal cord injuries
Authors: Olby Natasha J. , Risio Luisa De , Muñana Karen R. , Wosar Marc A. , Skeen Todd M. , Sharp Nick J.H. , Keene Bruce W.
Published: December 2005

Objective—To develop and compare the reliability of 2 methods of scoring pelvic limb gait in dogs recovering from thoracolumbar spinal cord injuries and to use this scoring system to determine the rate and level of functional recovery of dogs with acute thoracolumbar intervertebral disk herniations.

Animals—46 dogs with spinal cord injuries resulting from intervertebral disk herniations.

Procedure—Dogs' gaits were videotaped at different time intervals after injury. In phase 1 of the study, the stages of recovery of pelvic limb function were identified, and a numeric scoring system was devised to reflect that recovery. In phase 2, pelvic limb gait was scored by different observers, using a numeric and a visual analog scale. Intra- and interobserver coefficients of variability of both methods were compared. In phase 3, pelvic limb function was scored, using the numeric scale at various intervals after acute thoracolumbar disk herniations.

Results—The numeric scale was significantly more reliable than the visual analog scale when both intraand interobserver coefficients of variability were evaluated. Dogs that were paraplegic with no deep pain sensation recovered at different rates during the first 3 months, whereas dogs that were paraplegic with deep pain sensation typically recovered within 1 month of injury.

Conclusion and Clinical Relevance—Pelvic limb gait of dogs recovering from thoracolumbar spinal cord injuries can be reliably quantified, using a numeric scale. This scale will facilitate the performance of clinical trials aimed at improving the outcome of acute spinal cord injuries. (Am J Vet Res2001;62:1624–1628)
Effects of exercise on gastric volume and pH in the proximal portion of the stomach of horses
Authors: Lorenzo-Figueras Mireia , Merritt Alfred M.
Published: December 2005

Objective—To assess effects of exercise on a treadmill with changes in gastric volume and pH in the proximal portion of the stomach of horses.

Animals—3 healthy adult horses.

Procedure—A polyester bag of approximately 1,600 mL was placed into the proximal portion of the stomach of each horse via a nasogastric tube. Changes in bag volume, determined by an electronic barostat, were recorded before, during, and after a training session on a treadmill with and without prior withholding of food. In separate experiments, pH in the proximal portion of the stomach was continuously recorded during exercise for fed and food-withheld conditions. Finally, changes in intra-abdominal and intragastric pressure were simultaneously recorded during a training session.

Results—Bag volume rapidly decreased to nearly zero during trotting and galloping. Conversely, a return to walking resulted in a sharp increase in volume and a return to pre-exercise values. Intragastric and intraabdominal pressures increased almost in parallel with walking, trotting, galloping, and galloping on a slope. Gastric pH decreased rapidly to < 4 at the beginning of walking, continued to decrease during trotting and galloping, and remained low until a return to walking.

Conclusions and Clinical Relevance—Increased intra-abdominal pressure during intense exercise in horses causes gastric compression, pushing acidic contents into the proximal, squamous-lined region of the stomach. Increased duration of acid exposure directly related to daily duration of exercise may be the reason that squamous lesions tend to develop or worsen when horses are in intensive training programs. (Am J Vet Res2002;63:1481–1487)
Effects of initial handling and training on autonomic nervous function in young Thoroughbreds
Authors: Ohmura Hajime , Hiraga Atsushi , Aida Hiroko , Kuwahara Masayoshi , Tsubone Hirokazu
Published: December 2005

Objective—To determine the effects of initial handling and training on autonomic nervous functions in young Thoroughbreds.

Animals—63 healthy Thoroughbreds.

Procedure—All horses were trained to be handled and initially ridden in September of the yearling year and then trained until the following April by conventional training regimens. To obtain the heart rate (HR), electrocardiograms were recorded in the stable before initial handling and training and following 7 months of training; variations in HR were then evaluated from the power spectrum in terms of the low frequency (LF; 0.01 to 0.07 Hz) power and high frequency (HF; 0.07 to 0.6 Hz) power as indices of autonomic nervous activity. To evaluate the fitness, the V200 (velocity at HR of 200 beat/min), which is reflective of the aerobic capacity of the horse, was measured.

Results—Mean (± SE) resting HR decreased significantly from 41.5 ± 0.8 to 38.7 ± 0.4 beat/min following 7 months of training. The LF power of horses increased significantly from 1,037 ± 128 milliseconds2in September of the yearling year to 2,944 ± 223 milliseconds2in the following April. Similarly, the HF power increased significantly from 326 ± 30 milliseconds2to 576 ± 39 milliseconds2at the corresponding time points. The V200increased significantly following training.

Conclusions and Clinical Relevance—Increases in LF and HF powers indicate that parasympathetic nervous activity increases in horses by 7 months of training. The decrease in resting HR may be dependent on the training-induced increase of parasympathetic nervous activity in Thoroughbreds. (Am J Vet Res2002;63:1488–1491)
In vitro investigation of the effects of cyclooxygenase-2 inhibitors on contractile activity of the equine dorsal and ventral colon
Authors: Van Hoogmoed Linda M. , Snyder Jack R. , Harmon Faye A.
Published: December 2005

Objective—To evaluate the effect of 2 cyclooxygenase (COX)-2 inhibitors on contractile activity of the circular smooth muscle layer of the equine dorsal and ventral colon.

Sample Population—Samples of the dorsal and ventral colon obtained from 10 healthy horses.

Procedure—Full-thickness tissue samples were collected from the dorsal colon in the area of the diaphragmatic flexure and the ventral colon in the area of the sternal flexure. Samples were cut into strips oriented along the fibers of the circular muscle layer and mounted in a tissue bath system for determination of contractile strength. Incremental amounts of etodolac, nabumetone, and indomethacin were added, and contractile activity was recorded.

Results—Response of the dorsal and ventral colon to nonsteroidal anti-inflammatory drugs (NSAIDs) was variable. Indomethacin induced the greatest reduction in contractile activity, followed by nabumetone. For etodolac, the difference from baseline values was only significantly reduced at the highest concentration used (1 × 10–5M) for the ventral colon.

Conclusions and Clinical Relevance—The NSAIDs that are designed to target the COX-2 isoform appeared to have variable effects on the contractile activity of the equine dorsal and ventral colon. Etodolac appeared to have the least effect on contractile activity, compared with the effects attributable to nabumetone, and would potentially have the fewest adverse effects relative to motility of the dorsal and ventral colon. (Am J Vet Res2002;63:1496–1500)
In vitro biomechanical study of rotational stabilizers of the canine elbow joint
Authors: Talcott Kent W. , Schulz Kurt S. , Kass Philip H. , Mason David R. , Stover Susan M.
Published: December 2005

Objective—To develop a model for measuring rotary stability of the canine elbow joint and to evaluate the relative contribution of the anconeal process (AN), lateral collateral ligament (LCL), and medial collateral ligament (MCL).

Sample Population—18 forelimbs from 12 canine cadavers.

Procedure—Forelimbs were allocated to 3 experimental groups (6 forelimbs/group). Each intact forelimb was placed in extension at an angle of 135° and cycled 50 times from –16° (pronation) to +28° (supination) in a continuous manner at 2.0 Hz. Cycling was repeated following sectioning of the structure of interest (group 1, AN; group 2, LCL; and group 3, MCL). Torque at –12° (pronation) and +18° (supination) was measured for each intact and experimentally sectioned limb. A Student t test was performed to compare torque values obtained from intact verses experimentally sectioned limbs and for comparison with established criteria for differentiation of primary (≥ 33%), secondary (10 to 33%), and tertiary rotational stabilizers (< 10%).

Results—In pronation, the AN was the only primary stabilizer (65%). For supination, the LCL was a primary stabilizer (48%), AN was a secondary stabilizer (24%), and MCL was a tertiary stabilizer (7%).

Conclusions and Clinical Relevance—With the elbow joint in extension at an angle of 135°, the AN is a primary rotational stabilizer in pronation, and the LCL is a primary stabilizer in supination. Disruption of the AN or LCL may affect rotary range of motion or compromise stability of the elbow joint in dogs. (Am J Vet Res2002;63:1520–1526)
Aldose reductase activity and glucose-related opacities in incubated lenses from dogs and cats
Authors: Richter Marianne , Guscetti Franco , Spiess Bernhard
Published: December 2005

Objective—To determine responses of canine and feline lenses to incubation in a medium with a high glucose concentration.

Sample Population—Lenses from 35 dogs and 26 cats.

Procedure—Glucose concentrations were measured in paired lenses from 25 dogs and 17 cats after incubation for 14 days in high-glucose (30 mmol of glucose/ L) or control (6 mmol of glucose/L) medium. Aldose reductase activity was measured spectrophotometrically in the incubated lenses and in freshly frozen lenses from 10 dogs and 9 cats. Two lenses of each group were studied histologically.

Results—Canine and feline lenses in high-glucose medium developed glucose-specific opacities of variable localization and extent. Canine lenses developed equatorial vacuoles, but severity of the lesions was not associated with the age of the dog. Lenses from young cats (≤ 4 years old) developed extensive posterior cortical opacities, whereas those from older cats (> 4 years old) did not. Glucose concentrations were similar in all lenses incubated in high-glucose medium; however aldose reductase activity was significantly lower in lenses from older cats, compared with lenses from young cats and from dogs.

Conclusions and Clinical Relevance—High aldose reductase activity and glucose-related opacities suggest a central role for this enzyme in the pathogenesis of diabetic cataracts in dogs and cats. Because onset of diabetes mellitus usually occurs in cats > 7 years of age, low activity of aldose reductase in lenses of older cats may explain why diabetic cataracts are rare in this species despite hyperglycemia. (Am J Vet Res2002;63:1591–1597)
Pharmacokinetics of sulfamethoxazole and trimethoprim in donkeys, mules, and horses
Authors: Peck Kenneth E. , Matthews Nora S. , Taylor Tex S. , Mealey Katrina L.
Published: December 2005

Objective—To compare serum disposition of sulfamethoxazole and trimethoprim after IV administration to donkeys, mules, and horses.

Animals—5 donkeys, 5 mules, and 3 horses.

Procedure—Blood samples were collected before (time 0) and 5, 15, 30, and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 24 hours after IV administration of sulfamethoxazole (12.5 mg/kg) and trimethoprim (2.5 mg/kg). Serum was analyzed in triplicate with high-performance liquid chromatography for determination of sulfamethoxazole and trimethoprim concentrations. Serum concentration-time curve for each animal was analyzed separately to estimate noncompartmental pharmacokinetic variables.

Results—Clearance of trimethoprim and sulfamethoxazole in donkeys was significantly faster than in mules or horses. In donkeys, mean residence time (MRT) of sulfamethoxazole (2.5 hours) was less than half the MRT in mules (6.2 hours); MRT of trimethoprim in donkeys (0.8 hours) was half that in horses (1.5 hours). Volume of distribution at steady state (Vdss) for sulfamethoxazole did not differ, but Vdss of trimethoprim was significantly greater in horses than mules or donkeys. Area under the curve for sulfamethoxazole and trimethoprim was higher in mules than in horses or donkeys.

Conclusions and Clinical Relevance—Dosing intervals for IV administration of trimethoprim-sulfamethoxazole in horses may not be appropriate for use in donkeys or mules. Donkeys eliminate the drugs rapidly, compared with horses. Ratios of trimethoprim and sulfamethoxazole optimum for antibacterial activity are maintained for only a short duration in horses, donkeys, and mules. (Am J Vet Res2002;63:349–353)
Dynamics of porcine circovirus type 2 infection in a herd of pigs with postweaning multisystemic wasting syndrome
Authors: Rodríguez-Arrioja Gabriela M. , Segalés Joaquim , Calsamiglia Maria , Resendes Ana R. , Balasch Mònica , Plana-Durán Juan , Casal Jordi , Domingo Mariano
Published: December 2005

Objective—To determine the pattern of infection for
porcine circovirus type 2 (PCV2) in a herd of pigs with
postweaning multisystemic wasting syndrome
(PMWS).

Animals—29 sows and 250 pigs.

Procedure—Blood samples were collected from all
3-, 7-, and 12-week old pigs and 59 pigs at 28 weeks
of age. Pigs that died during the study were necropsied.
Porcine parvovirus and PCV2 antibodies were
assayed. A polymerase chain reaction (PCR) was
used to detect PCV2 genome in serum of selected
pigs.

Results—The PMWS started when pigs were 8
weeks old, with a prevalence of 30% in 8- to 10-weekold
pigs. Eighty-three pigs died during the period
between 3 and 12 weeks of age. Microscopic lesions
consistent with PMWS were observed, and PCV2
nucleic acid was detected (50 of 68 pigs). Antibodies
to PCV2 decreased from 3 to 7 weeks of age,
increased at 12 weeks of age, and were maintained
until 28 weeks of age. One sow had a positive result
for PCR of serum. Nine, 37, and 8 pigs had PCV2
genome in serum obtained at 7, 12, and 28 weeks of
age, respectively.

Conclusions and Clinical Relevance—Infection with
PCV2 coincided with severe clinical signs; however,
infected 28-week-old pigs did not have evidence of
disease. Immunity declined over time in young pigs.
A long duration of PCV2 viremia was apparent in a
high percentage of infected pigs, which may affect
transmission and persistence of the virus in a herd.
(Am J Vet Res 2002;63:354–357).
Effects of pentoxifylline on pulmonary function and results of cytologic examination of bronchoalveolar lavage fluid in horses with recurrent airway obstruction
Authors: Léguillette Renaud , Désévaux Cyril , Lavoie Jean-Pierre
Published: December 2005

Objectives—To determine the effects of pentoxifylline (PTX) administration on lung function and results of cytologic examination of bronchoalveolar lavage fluid in horses affected by recurrent airway obstruction (RAO).

Animals—10 RAO-affected horses.

Procedures—6 horses were orally administered PTX (16 g) mixed with corn syrup, and 4 horses were administered corn syrup alone, twice daily for 14 days. Pulmonary function was evaluated before administration (day 0) and on days 8 and 15. Bronchoalveolar lavage (BAL) was performed on days 0 and 15. Reversibility of airway obstruction was assessed by measuring pulmonary function before and after administration of atropine (0.02 mg/kg, IV). Serum concentration of PTX was measured in 4 horses 30 minutes and 2 and 4 hours after administration of PTX on days 1, 2, 3, 7, and 14.

Results—Administration of PTX to RAO-affected horses resulted in a decrease in elastance value on day 8 and on elastance and resistance (RL) values on days 8 and 15. Results for cytologic examination of BAL fluid obtained on day 15 did not differ significantly, compared with values for day 0. Values of RLdecreased in all horses following administration of atropine. When mixed in corn syrup and administered orally, PTX was poorly absorbed in horses, and there was noticeable variation in serum PTX concentrations over time and among horses.

Conclusions and Clinical Relevance—Based on these results, it can be concluded that administration of PTX at high doses improved respiratory function of RAO-affected horses maintained in an unfavorable environment. (Am J Vet Res2002;63:459–463)
Protein sorting upon exit from the endoplasmic reticulum dominates Golgi biogenesis in budding yeast
Authors: Sasaki Saku , Schlarmann Philipp , Hanaoka Kazuki , Nishii Hinako , Moriya Hisao , Muñiz Manuel , Funato Kouichi
Published: February 2024

Cells sense and control the number and quality of their organelles, but the underlying mechanisms of this regulation are not understood. Our recent research in the yeast Saccharomyces cerevisiae has shown that long acyl chain ceramides in the endoplasmic reticulum (ER) membrane and the lipid moiety of glycosylphosphatidylinositol (GPI) anchor determine the sorting of GPI‐anchored proteins in the ER. Here, we show that a mutant strain, which produces shorter ceramides than the wild‐type strain, displays a different count of Golgi cisternae. Moreover, deletions of proteins that remodel the lipid portion of GPI anchors resulted in an abnormal number of Golgi cisternae. Thus, our study reveals that protein sorting in the ER plays a critical role in maintaining Golgi biogenesis.
Cryo‐EM structure of the inactive ribosome complex accumulated in chick embryo cells in cold‐stress conditions
Authors: Nurullina Liliia , Terrosu Salvatore , Myasnikov Alexander G. , Jenner Lasse Bohl , Yusupov Marat
Published: February 2024

Here, we present the high‐resolution structure of the Gallus gallus 80S ribosome obtained from cold‐treated chicken embryos. The translationally inactive ribosome complex contains elongation factor eEF2 with GDP, SERPINE1 mRNA binding protein 1 (SERBP1) and deacylated tRNA in the P/E position, showing common features with complexes already described in mammals. Modeling of most expansion segments of G. gallus 28S ribosomal RNA allowed us to identify specific features in their structural organization and to describe areas where a marked difference between mammalian and avian ribosomes could shed light on the evolution of the expansion segments. This study provides the first structure of an avian ribosome, establishing a model for future structural and functional studies on the translational machinery in Aves.
STING activator 2′3′‐cGAMP enhanced HSV‐1‐based oncolytic viral therapy
Authors: Sibal Patricia Angela , Matsumura Shigeru , Ichinose Toru , Bustos‐Villalobos Itzel , Morimoto Daishi , Eissa Ibrahim R. , Abdelmoneim Mohamed , Aboalela Mona Alhussein Mostafa , Mukoyama Nobuaki , Tanaka Maki , Naoe Yoshinori , Kasuya Hideki
Published: February 2024

Oncolytic viruses (OVs) can selectively replicate in tumor cells and remodel the microenvironment of immunologically cold tumors, making them a promising strategy to evoke antitumor immunity. Similarly, agonists of the stimulator of interferon genes (STING)‐interferon (IFN) pathway, the main cellular antiviral system, provide antitumor benefits by inducing the activation of dendritic cells (DC). Considering how the activation of the STING‐IFN pathway could potentially inhibit OV replication, the use of STING agonists alongside OV therapy remains largely unexplored. Here, we explored the antitumor efficacy of combining an HSV‐1‐based OV, C‐REV, with a membrane‐impermeable STING agonist, 2′3′‐GAMP. Our results demonstrated that tumor cells harbor a largely defective STING‐IFN pathway, thereby preventing significant antiviral IFN induction regardless of the permeability of the STING agonist. In vivo, the combination therapy induced more proliferative KLRG1‐high PD1‐low CD8+ T‐cells and activated CD103+ DC in the tumor site and increased tumor‐specific CD44+ CD8+ T‐cells in the lymph node. Overall, the combination therapy of C‐REV with 2′3′‐cGAMP elicited antitumor immune memory responses and significantly enhanced systemic antitumor immunity in both treated and non‐treated distal tumors.
Regulation and tumor‐suppressive function of the miR‐379/miR‐656 (C14MC) cluster in cervical cancer
Authors: Srinath Sriharikrishnaa , Jishnu Padacherri Vethil , Varghese Vinay Koshy , Shukla Vaibhav , Adiga Divya , Mallya Sandeep , Chakrabarty Sanjiban , Sharan Krishna , Pandey Deeksha , Chatterjee Aniruddha , Kabekkodu Shama Prasada
Published: February 2024

Cervical cancer (CC) is a key contributor to cancer‐related mortality in several countries. The identification of molecular markers and the underlying mechanism may help improve CC management. We studied the regulation and biological function of the chromosome 14 microRNA cluster (C14MC; miR‐379/miR‐656) in CC. Most C14MC members exhibited considerably lower expression in CC tissues and cell lines in The Cancer Genome Atlas (TCGA) cervical squamous cell carcinoma and endocervical adenocarcinoma patient cohorts. Bisulfite Sanger sequencing revealed hypermethylation of the C14MC promoter in CC tissues and cell lines. 5‐aza‐2 deoxy cytidine treatment reactivated expression of the C14MC members. We demonstrated that C14MC is a methylation‐regulated miRNA cluster via artificial methylation and luciferase reporter assays. C14MC downregulation correlated with poor overall survival and may promote metastasis. C14MC activation via the lentiviral‐based CRISPRa approach inhibited growth, proliferation, migration, and invasion; enhanced G2/M arrest; and induced senescence. Post‐transcriptional regulatory network analysis of C14MC transcriptomic data revealed enrichment of key cancer‐related pathways, such as metabolism, the cell cycle, and phosphatidylinositol 3‐kinase (PI3K)–AKT signaling. Reduced cell proliferation, growth, migration, invasion, and senescence correlated with the downregulation of active AKT, MYC, and cyclin E1 (CCNE1) and the overexpression of p16, p21, and p27. We showed that C14MC miRNA activation increases reactive oxygen species (ROS) levels, intracellular Ca2+ levels, and lipid peroxidation rates, and inhibits epithelial–mesenchymal transition (EMT). C14MC targets pyruvate dehydrogenase kinase‐3 (PDK3) according to the luciferase reporter assay. PDK3 is overexpressed in CC and is inversely correlated with C14MC. Both miR‐494‐mimic transfection and C14MC activation inhibited PDK3 expression. Reduced glucose uptake and lactate production, and upregulation of PDK3 upon C14MC activation suggest the potential role of these proteins in metabolic reprogramming. Finally, we showed that C14MC activation may inhibit EMT signaling. Thus, C14MC is a tumor‐suppressive and methylation‐regulated miRNA cluster in CC. Reactivation of C14MC can be useful in the management of CC.
Phenotypic variation of FXN compound heterozygotes in a Friedreich ataxia cohort
Authors: Shen Megan M. , Rummey Christian , Lynch David R.
Published: February 2024

Objective

Most individuals with Friedreich ataxia (FRDA) have homozygous GAA triplet repeat expansions in the FXN gene, correlating with a typical phenotype of ataxia and cardiomyopathy. A minority are compound heterozygotes carrying a GAA expansion on one allele and a mutation on the other. The study aim was to examine phenotypic variation among compound heterozygotes.

Methods

Data on FXN mutations were obtained from the Friedreich Ataxia Clinical Outcome Measures Study (FA‐COMS). We compared clinical features in a single‐site FA‐COMS cohort of 51 compound heterozygous and 358 homozygous patients, including quantitative measures of cardiac, neurologic, and visual disease progression.

Results

Non‐GAA repeat mutations were associated with reduced cardiac disease, and patients with minimal/no function mutations otherwise had a typical FRDA phenotype but with significantly more severe progression. The partial function mutation group was characterized by relative sparing of bulbar and upper limb function, as well as particularly low cardiac involvement. Other clinical features in this group, including optic atrophy and diabetes mellitus, varied widely depending on the specific type of partial function mutation.

Interpretation

These data support that the typical FRDA phenotype is driven by frataxin deficiency, especially severe in compound heterozygotes with minimal/no function mutations, whereas the heterogeneous presentations of those with partial function mutations may indicate other contributing factors to FRDA pathogenesis.
Predicting the impact of CPAP on brain health: A study using the sleep EEG‐derived brain age index
Authors: Yook Soonhyun , Park Hea Ree , Joo Eun Yeon , Kim Hosung
Published: February 2024

Objective

This longitudinal study investigated potential positive impact of CPAP treatment on brain health in individuals with obstructive sleep Apnea (OSA). To allow this, we aimed to employ sleep electroencephalogram (EEG)‐derived brain age index (BAI) to quantify CPAP's impact on brain health and identify individually varying CPAP effects on brain aging using machine learning approaches.

Methods

We retrospectively analyzed CPAP‐treated (n = 98) and untreated OSA patients (n = 88) with a minimum 12‐month follow‐up of polysomnography. BAI was calculated by subtracting chronological age from the predicted brain age. To investigate BAI changes before and after CPAP treatment, we compared annual ΔBAI between CPAP‐treated and untreated OSA patients. To identify individually varying CPAP effectiveness and factors influencing CPAP effectiveness, machine learning approaches were employed to predict which patient displayed positive outcomes (negative annual ΔBAI) based on their baseline clinical features.

Results

CPAP‐treated group showed lower annual ΔBAI than untreated (−0.6 ± 2.7 vs. 0.3 ± 2.6 years, p < 0.05). This BAI reduction with CPAP was reproduced independently in the Apnea, Bariatric surgery, and CPAP study cohort. Patients with more severe OSA at baseline displayed more positive annual ΔBAI (=accelerated brain aging) when untreated and displayed more negative annual ΔBAI (=decelerated brain aging) when CPAP‐treated. Machine learning models achieved high accuracy (up to 86%) in predicting CPAP outcomes.

Interpretation.

CPAP treatment can alleviate brain aging in OSA, especially in severe cases. Sleep EEG‐derived BAI has potential to assess CPAP's impact on brain health. The study provides insights into CPAP's effects and underscores BAI‐based predictive modeling's utility in OSA management.
There and Back Again: Building Systems That Integrate, Interface, and Interact with the Human Body
Authors: Boys Alexander J.
Published: February 2024

Since Dr. Theodor Schwann posed the extension of Cell Theory to mammals in 1839, scientists have dreamt up ways to interface with and influence the cells. Recently, considerable ground in this area is gained, particularly in the scope of bioelectronics. New advances in this area have provided with a means to record electrical activity from cells, examining neural firing or epithelial barrier integrity, and stimulate cells through applied electrical fields. Many of these applications utilize invasive implantation systems to perform this interaction in close proximity to the cells in question. Traditionally, the body's immune system fights back against these systems through the foreign body response, limiting the efficacy of long‐term interactions. New technologies in tissue engineering, biomaterials science, and bioelectronics offer the potential to circumvent the foreign body response and create stable long‐term biological interfaces. Looking ahead, the next advancements in the biomedical sciences can truly integrate, interface, and interact with the human body.
Leveraging Crystallization Pathway to Control Structure in Hf0.5Zr0.5O2 Nanoparticles
Authors: Anguish Evan A. M. , Andrew Jennifer S.
Published: February 2024

Hf0.5Zr0.5O2‐based materials have garnered significant attention for applications requiring ferroelectricity at the nanoscale. This behavior arises due to the stabilization of metastable phases at room temperature. However, the synthesis of phase pure Hf0.5Zr0.5O2 remains a challenging problem in both thin films and nanoparticles. Herein, the crystallization of Hf0.5Zr0.5O2 nanoparticles from an as‐synthesized amorphous phase is studied. By tailoring the aggregate nature of the intermediate amorphous nanoparticles via different drying processes, the crystallization pathway can be altered, resulting in significant differences in crystal structure, crystallite size, and crystallite morphology after calcination. X‐ray diffraction (XRD) and Rietveld refinement show the dominant crystallographic phase changes from a monoclinic structure to a cubic structure for samples with decreased aggregation. Samples prepared via freeze drying exhibit the most aggregation control and correspond with the observation of single‐crystalline particle aggregates and branching structures attributed to a crystallization by particle attachment mechanism. Herein, differing crystallization pathways lead to unique crystal morphologies that stabilize the traditionally high‐temperature phases of Hf0.5Zr0.5O2‐based materials that are necessary for functional applications.
The Effect of Graphite Flake Volume Fraction on the Thermophysical Proper Ties of Graphite Flake/Aluminum Composites
Authors: Chi Qingbo , Du Xiaoming , Sun Zhendong , Li Siyu , Liu Fengguo
Published: February 2024

A vacuum hot‐press sintering process is utilized to manufacture graphite flake/aluminum composites, and the influence of graphite flake volume fraction on the microscopic structure, hardness, thermal conductivity (TC), and coefficient of thermal expansion (CTE) of the composites is investigated. The results indicate that the graphite flakes are neatly aligned along the in‐plane direction in the composites and exhibit a strong bond with the aluminum matrix interface. The in‐plane TC of the composite significantly increases with the addition of graphite flakes, whereas hardness, through‐plane TC, and CTE decrease. As the volume fraction of graphite flakes in the composites increases from 15% to 60%, in‐plane TC improves from 278.8 to 353.8 W m−1 K−1, through‐plane TC decreases from 164.4 to 33.2 W m−1 K−1, and the CTE decreases to 13.7 × 10−6 K−1, achieving high thermal conductivity and a low CTE.
Design and Selection of High Entropy Alloys for Hardmetal Matrix Applications Using a Coupled Machine Learning and Calculation of Phase Diagrams Methodology
Authors: Berry Joshua , Snell Robert , Anderson Magnus , Owen Lewis R. , Messé Olivier M. D. M. , Todd Iain , Christofidou Katerina A.
Published: February 2024

This study aims to utilize a combined machine learning (ML) and CALculation of PHAse Diagrams (CALPHAD) methodology to design hardmetal matrix phases for metal‐forming applications that can serve as the basis for carbide reinforcement. The vast compositional space that high entropy alloys (HEAs) occupy offers a promising avenue to satisfy the application design criteria of wear resistance and ductility. To efficiently explore this space, random forest ML models are constructed and trained from publicly available experimental HEA databases to make phase constitution and hardness predictions. Interrogation of the ML models constructed reveals accuracies >78.7% and a mean absolute error of 66.1 HV for phase and hardness predictions respectively. Six promising alloy compositions, extracted from the ML predictions and CALPHAD calculations, are experimentally fabricated and tested. The hardness predictions are found to be systematically under‐ and overpredicted depending on the alloy microstructure. In parallel, the phase classification models are found to lack sensitivity toward additional intermetallic phase formation. Despite the discrepancies identified between ML and experimental results, the fabricated compositions show promise for further experimental evaluation. These discrepancies are believed to be directly associated with the available databases but, importantly, have highlighted several avenues for both ML and database development.
Interventional Hydrogel Microsphere Controlled‐Releasing Curcumin for Photothermal Therapy against Endometriosis
Authors: Liu Xuemin , Yan Shengtao , Wu Hongliang , Chen Ming , Dai Hao , Wang Zhenxing , Chai Muyuan , Hu Qingyu , Li Dongdong , Chen Lei , Diao Ruiying , Chen Shi , Wang Liping , Shi Xuetao
Published: February 2024

Endometriosis is a prevalent gynecological disorder characterized by the presence of endometrial‐like tissue outside the uterus, causing chronic pelvic pain, painful periods, and infertility. Despite the common use of hormone therapy and surgical lesion excision in its treatment, there remain significant postoperative risks and potential side effects, with a high recurrence rate. An efficient nonsurgical treatment for this condition is therefore urgently needed. In this study, an interventional hydrogel microsphere with near‐infrared (NIR)‐controlled curcumin release is developed for the non‐invasive thermal therapy of endometriosis. The hydrogel microspheres demonstrate good biocompatibility and photothermal activities, causing the death of endometrial stromal cells under NIR and controlled curcumin (Cur) release. When injected into endometriotic lesions and stimulated by NIR light, the interventional hydrogel microspheres (Cur‐FeHMPs) can raise the temperature of the endometriotic lesions to 43.65 °C, inducing endometriotic lesion elimination. Furthermore, the controlled curcumin release from the interventional hydrogel inhibits the proinflammatory environment in endometriosis. The Cur‐FeHMPs in combination with NIR present a novel strategy for endometriosis treatment.
Surface Modification of Nerve Guide Conduits with ECM Coatings and Investigating Their Impact on Schwann Cell Response
Authors: Pinzon‐Herrera Luis , Magness John , Apodaca‐Reyes Hector , Sanchez Jesus , Almodovar Jorge
Published: February 2024

In this study, layer‐by‐layer coatings composed of heparin and collagen are proposed as an extracellular mimetic environment on nerve guide conduits (NGC) to modulate the behavior of Schwann cells (hSCs). The authors evaluated the stability, degradation over time, and bioactivity of six bilayers of heparin/collagen layer‐by‐layer coatings, denoted as (HEP/COL)6. The stability study reveals that (HEP/COL)6 is stable after incubating the coatings in cell media for up to 21 days. The impact of (HEP/COL)6 on hSCs viability, protein expression, and migration is evaluated. These assays show that hSCs cultured in (HEP/COL)6 have enhanced protein expression and migration. This condition increases the expression of neurotrophic and immunomodulatory factors up to 1.5‐fold compared to controls, and hSCs migrated 1.34 times faster than in the uncoated surfaces. Finally, (HEP/COL)6 is also applied to a commercial collagen‐based NGC, NeuraGen, and hSC viability and adhesion are studied after 6 days of culture. The morphology of NeuraGen is not altered by the presence of (HEP/COL)6 and a nearly 170% increase of the cell viability is observed in the condition where NeuraGen is used with (HEP/COL)6. Additionally, cell adhesion on the coated samples is successfully demonstrated. This work demonstrates the reparative enhancing potential of extracellular mimetic coatings.
Synergistic Brilliance: Engineered Bacteria and Nanomedicine Unite in Cancer Therapy
Authors: Zhou Yaofeng , Li Qianying , Wu Yuhao , Zhang Wan , Ding Lu , Ji Chenlin , Li Ping , Chen Tingtao , Feng Lili , Tang Ben Zhong , Huang Xiaolin
Published: February 2024

Engineered bacteria are widely used in cancer treatment because live facultative/obligate anaerobes can selectively proliferate at tumor sites and reach hypoxic regions, thereby causing nutritional competition, enhancing immune responses, and producing anticancer microbial agents in situ to suppress tumor growth. Despite the unique advantages of bacteria‐based cancer biotherapy, the insufficient treatment efficiency limits its application in the complete ablation of malignant tumors. The combination of nanomedicine and engineered bacteria has attracted increasing attention owing to their striking synergistic effects in cancer treatment. Engineered bacteria that function as natural vehicles can effectively deliver nanomedicines to tumor sites. Moreover, bacteria provide an opportunity to enhance nanomedicines by modulating the TME and producing substrates to support nanomedicine‐mediated anticancer reactions. Nanomedicine exhibits excellent optical, magnetic, acoustic, and catalytic properties, and plays an important role in promoting bacteria‐mediated biotherapies. The synergistic anticancer effects of engineered bacteria and nanomedicines in cancer therapy are comprehensively summarized in this review. Attention is paid not only to the fabrication of nanobiohybrid composites, but also to the interpromotion mechanism between engineered bacteria and nanomedicine in cancer therapy. Additionally, recent advances in engineered bacteria‐synergized multimodal cancer therapies are highlighted.
High‐Index and Low‐Loss Topological Insulators for Mid‐Infrared Nanophotonics: Bismuth and Antimony Chalcogenides
Authors: Menabde Sergey G. , Heiden Jacob T. , Zenin Vladimir A. , Mortensen N. Asger , Jang Min Seok
Published: February 2024

Topological insulators generally have dielectric bulk and conductive surface states. Consequently, some of these materials are shown to support polaritonic modes at visible and THz frequencies. At the same time, the optical properties of topological insulators in the mid‐infrared (mid‐IR) remain poorly investigated. Here, near‐field imaging is employed to probe the mid‐IR response from the exfoliated flakes of bismuth (Bi)/selenide (Se)/telluride (Te)/antimony (Sb) crystals with varying stoichiometry – Bi2Se3, Bi2Te2Se, and Bi1.5Sb0.5Te1.7Se1.3 – in pristine form as well as covered by thin flakes of hexagonal boron nitride (hBN) is employed. Contrary to theoretical expectations, all three materials exhibit a dielectric response with a high refractive index and with a loss below the experimental detection limit. Particularly, the near‐field mapping of propagating phonon‐polaritons in hBN demonstrates that all three van der Waals crystals with different stoichiometry act as a practically lossless dielectric substrate with an ultra‐high refractive index of up to 7.5 in Bi2Te2Se. Such a unique dielectric crystal will be of great advantage for numerous nanophotonic applications in the mid‐IR.
Ubiquitous Aluminum(III)‐TADF Complex as Sensitizer for Highly Efficient Solution‐Processed Hyperfluorescent OLEDs with Narrow Emission
Authors: Hoshi Keigo , Sasabe Hisahiro , Chiba Yudai , Yoshida Naoto , Nakamura Takeru , Nagasawa Keisuke , Sayama Yuya , Katagiri Hiroshi , Kido Junji
Published: February 2024

Although Earth‐abundant, ubiquitous, metal‐based thermally activated delayed fluorescence (TADF) complexes are among the most promising candidate materials for next‐generation organic light‐emitting devices (OLEDs), few complexes are explored. Herein, a highly emissive aluminum(III)‐TADF complex—Al(MCzDBM)3—with three β‐diketone ligands is presented as a sensitizer for multiresonance (MR)‐TADF emitters. This complex exhibited green emission with suitable photophysical functions as a sensitizer, such as a high photoluminescent quantum yield (PLQY) of up to 97% with reduced aggregation‐caused quenching, a high radiative rate constant (kr) of 5.6 × 107 s−1, and a short delayed lifetime (τd) of 4.0 µs in the solid state. A solution‐processed Al(MCzDBM)3‐based OLED exhibited an external quantum efficiency (EQE) of 23.6%. This complex sensitized a yellow MR‐TADF emitter, yielding a near‐unity PLQY, and is used to fabricate a solution‐processed hyperfluorescent OLED with an EQE of 21.6% and full width at half maximum of 45 nm.
Generalized Drude–Lorentz Model Complying with the Singularity Expansion Method
Authors: Ben Soltane Isam , Dierick Félice , Stout Brian , Bonod Nicolas
Published: February 2024

Deriving analytical expressions of dielectric permittivities is required for numerical and physical modeling of optical systems and the soar of non‐Hermitian photonics motivates their prolongation in the complex plane. Analytical models are based on the association of microscopic models to describe macroscopic effects. However, the question is to know whether the resulting Debye–Drude–Lorentz models are not too restrictive. Here, it is shown that the permittivity must be treated as a meromorphic transfer function that complies with the requirements of complex analysis. This function can be naturally expanded on a set of complex singularities. This singularity expansion of the dielectric permittivity allows to derive a generalized expression of the Debye–Drude–Lorentz model that complies with the requirements of complex analysis and the constraints of physical systems. It is shown that the complex singularities and other parameters of this generalized expression can be retrieved from experimental data acquired along the real frequency axis. The accuracy of this expression is assessed for a wide range of materials including metals, 2D materials and dielectrics, and it is shown how the distribution of the retrieved poles helps in characterizing the materials.
Defibrillated Lignocellulose Recovery Guided by Plant Chemistry and Anatomy – A Pioneering Study with Lupinus angustifolius
Authors: Schmidt Alina E.M. , Choong Ferdinand X. , Richter‐Dahlfors Agneta , Edlund Ulrica
Published: February 2024

The strive toward sustainability increases the demand for bio‐based material production, forcing expansion of the biorefinery feedstock supply from forest wood to non‐woody materials such as agricultural residues. As a model organism for legume crops, the aptness of agricultural lupins as a lignocellulose feedstock is investigated. Principle chemical analysis combined with optotracing, in which the fluorescent tracer molecule Carbotrace 680 generates a visual map of the native tissues’ lignocellulose anatomy at sub‐cellular resolution, enables informed design of a mild recovery process. A streamlined conversion approach is then designed, yielding lignin‐containing microfibrillated cellulose. By monitoring defibrillation and delignification throughout the extraction process, the use of optotracing for non‐destructive fiber analytics at unprecedented details across all hierarchical structures of lignocellulosic materials is demonstrated. This crop valorization is a prime illustration of a holistic use of lupin biomass, with seeds serving as plant‐based food sources, and other parts as sources for lignocellulose‐based materials, thereby expanding both the biorefinery concept and feedstock supply.
Experimental and Computational Study of Mg and Ta‐Doped Li7La3Zr2O12 Garnet‐Type Solid Electrolytes for All‐Solid‐State Lithium Batteries
Authors: Ma Kai , Chen Bowen , Li Cheng‐Xin , Thangadurai Venkataraman
Published: February 2024

Garnet‐type Li7La3Zr2O12 electrolytes have garnered significant attention as promising solid‐state electrolyte candidates in all‐solid‐state lithium batteries (ASSLBs). However, its susceptibility to forming Li2CO3 upon atmospheric exposure leads to performance degradation, limiting its application. This study introduces a co‐doping strategy of Mg and Ta to enhance the properties of garnet electrolytes. Pure cubic Mg and Ta‐doped LLZO electrolytes are successfully synthesized using the solid‐state reaction method. Experimental results, coupled with density functional theory (DFT) calculation, reveal that Mg2+ doping occurs primarily at the La site (24c). This substitution, given the substantial disparity in ionic radii between Mg2+ and La3+, effectively narrows the transport bottleneck for Li‐ions, resulting in a decreased ionic conductivity and an increased activation energy. Li6.6La2.8Mg0.2Zr1.4Ta0.6O12 exhibits a relative density of ≈92.6%, demonstrating outstanding performance with a room temperature ionic conductivity of 4.31 × 10−4 S cm−1 and low electronic conductivity of 2.48 × 10−8 S cm−1. Notably, after 4 months of atmospheric exposure, its ionic conductivity decreased to ≈78% of the initial value, attributable to Li2CO3 formation. Furthermore, the material demonstrated exceptional long‐term cycle stability over 1000 h at a current density of 0.1 mA cm−2 at 25 °C, indicating effective suppression of Li dendrite formation.