bluuebunny/crossref_metadata_2025 huggingface dataset:
Macrophage foam cell-derived mediator promotes spontaneous fat lipolysis in atherosclerosis models
Authors: Banerjee Dipanjan , Patra Debarun , Sinha Archana , Chakrabarty Dwaipayan , Patra Aparup , Sarmah Raktim , Dey Upalabdha , Dutta Rajdeep , Bhagabati Sarada K , Mukherjee Ashis K , Kumar Aditya , Pal Durba , Dasgupta Suman
Published: November 2024

Ectopic lipid accumulation in macrophages is responsible for the formation of macrophage foam cells (MFCs) which are involved in the crosstalk with the perivascular adipose tissue (PVAT) of the vascular wall that plays a pivotal role in the progression of atherosclerosis. However, the interrelationship between MFCs and PVAT implementing adipocyte dysfunction during atherosclerosis has not yet been established. We hypothesized that MFC-secreted mediator(s) is causally linked with PVAT dysfunction and the succession of atherosclerosis. To test this hypothesis, MFCs were cocultured with adipocytes, or the conditional media of MFCs (MFC-CM) were exposed to adipocytes and found a significant induction of fat lipolysis in adipocytes. The molecular filtration followed by the high-performance liquid chromatography (HPLC) fractionation and liquid chromatography-mass spectrometry/mass spectrometry (LC–MS/MS) analysis of MFC-CM revealed a novel mediator fetuin-A (FetA) that significantly augments toll-like receptor 4 (TLR4)-dependent fat lipolysis in adipocytes. Mechanistically, MFC-derived FetA markedly increased TLR4-dependent c-Jun N-terminal kinases (JNK)/extracellular signal-regulated kinases (ERK) activation that causes spontaneous fat lipolysis implementing adipocyte dysfunction. Thus, the present study provides the first evidence of MFC-derived FetA that induces adipocyte dysfunction by the stimulation of spontaneous fat lipolysis. Therefore, targeting the crosstalk between MFCs and adipocytes could be a newer approach to counter the progression of atherosclerosis.
Orbital motion of gold heterodimer driven by optical force of circularly polarized light and reactive drag of medium
Authors: Ku Yun-Cheng , Yang Yao-Sheng , Kuo Mao-Kuen , Liaw Jiunn-Woei
Published: November 2024

This theoretical study explores the two-dimensional orbital motion of an optically bound heterodimer consisting of two gold nanoparticles (NPs) of different sizes, driven by circularly polarized (CP) light. Although a CP light possesses only spin angular momentum without orbital angular momentum, it can still induce orbital revolution in the plasmonic heterodimer. This phenomenon arises from the interaction between the optical force and torque generated by the CP light and the reactive drag force and torque from the surrounding medium. We calculate the optical forces acting on each NP by analyzing the Maxwell stress tensor at their surfaces, and we account for the reactive drag force using Stokes’ law. These forces are used to simulate the trajectories of the NPs through dynamic equations of motion. Our results demonstrate that, regardless of the initial conditions of the two NPs, they will become optically bound together, exhibiting rigid-body translation and rotation. Notably, the center of mass of the heterodimer undergoes an orbital revolution around a fixed point eventually. The CP light-manipulated heterodimer behaves like a boomerang, acting as a spinning rotor on a circular path. The heterodimer's orbital radius and direction of revolution are influenced by the size disparity between the two NPs. Additionally, each NP experiences spin motion, with the spin direction determined by the handedness of the CP light. The optically bound gold heterodimer functions as a light-driven microrotor, with potential applications in microfluidic channels. These findings offer valuable insights into the optomechanical manipulation of non-monodisperse NP clusters using CP light.
Legged robot locomotion on viscoelastic terrain using a reduced-order dynamic model with rolling contact and energy input and dissipation
Authors: Wang Tso-Kang , Lin Pei-Chun
Published: November 2024

In recent decades, robots have gradually taken on more tasks that require mobility. However, unlike animals that are capable of coordinating complex sensing organs and muscles to achieve dynamic motion on all kinds of terrains, robots have difficulties traversing rough terrains at high speeds due to limitations of computational resources, actuator strength, etc. This research aims to build a new model that captures the essence of how animals achieve dynamic motion and traverse rough terrains. Based on the previously developed dynamic model running on the rigid ground, this model incorporates the interaction between the leg and the ground, which is described by a combination of linear springs and dampers that can model a wide range of terrains. Simulation results show chaotic behavior under certain conditions, and an experiment verified such behavior. This work underscores the urgency and significance of understanding and replicating the capabilities of animals in robot locomotion, and its relevance to the field of robotics is significant.
Stellar surface information from the Ca ii H&K lines – II. Defining better activity proxies
Authors: Cretignier M , Hara N C , Pietrow A G M , Zhao Y , Yu H , Dumusque X , Sozzetti A , Lovis C , Aigrain S
Published: November 2024

In our former paper I, we showed on the Sun that different active regions possess unique intensity profiles on the Ca ii H & K lines. We now extend the analysis by showing how those properties can be used on real stellar observations, delivering more powerful activity proxies for radial velocity correction. More information can be extracted on rotational time-scale from the Ca ii  H & K lines than the classical indicators: S-index and $\log (R^{^{\prime }}_{\text{HK}})$. For high-resolution HARPS observations of $\alpha$ Cen B, we apply a principal and independent component analysis on the Ca ii  H & K spectra time-series to disentangle the different sources that contribute to the disc-integrated line profiles. While the first component can be understood as a denoised version of the Mount-Wilson S-index, the second component appears as powerful activity proxies to correct the radial velocities induced by the inhibition of the convective blueshift in stellar active regions. However, we failed to interpret the extracted component into a physical framework. We conclude that a more complex kernel or bandpass than the classical triangular of the Mount Wilson convention should be used to extract activity proxies. To this regard, we provide the first principal component activity profile obtained across the spectral type sequence between M1V to F9V type stars.
Conjugation Mediates Large-Scale Chromosomal Transfer in Streptomyces Driving Diversification of Antibiotic Biosynthetic Gene Clusters
Authors: Choufa Caroline , Gascht Pauline , Leblond Hugo , Gauthier Anthony , Vos Michiel , Bontemps Cyril , Leblond Pierre
Published: November 2024

Streptomyces are ubiquitous soil-dwelling bacteria with large, linear genomes that are of special importance as a source of metabolites used in human and veterinary medicine, agronomy, and industry. Conjugative elements (actinomycetes integrative and conjugative elements, AICEs) are the main drivers of Streptomyces Horizontal Gene Transfer. AICE transfer has long been known to be accompanied by mobilization of chromosomal DNA. However, the magnitude of DNA transfer, or the localization of acquired DNA across their linear chromosome, has remained undetermined. We here show that conjugative crossings in sympatric strains of Streptomyces result in the large-scale, genome-wide distributed replacement of up to one-third of the recipient chromosome, a phenomenon for which we propose the name “Streptomyces Chromosomal Transfer” (SCT). Such chromosome blending results in the acquisition, loss, and hybridization of Specialized Metabolite Biosynthetic Gene Clusters, leading to a novel metabolic arsenal in exconjugant offspring. Harnessing conjugation-mediated specialized metabolite biosynthesis gene cluster diversification holds great promise in the discovery of new bioactive compounds including antibiotics.
Industrial reform policies: does marketization enhance productivity more than privatization?
Authors: Chen Yang , He Ming , Rudkin Simon , Webber Don J
Published: November 2024

Placing state-owned firms into the private sector is understood to yield productivity gains, but this effect is seldom decomposed into changes in ownership (privatization) and changes in firm characteristics to match privately owned firms without changing ownership (marketization). This article presents an empirical assessment of Chinese firm-level data using a counterfactual design approach to identify if the Chinese ‘grasp the large and let go of the small’ industrial policy reform initiative reduced the efficiency gap between state-owned and non-state-owned enterprises and whether any gains were associated with privatization or marketization. Our empirical results show that marketization was associated with stronger increases in productivity than was privatization, suggesting that industrial reforms should consolidate assets, enhance cash flows, and reduce the need for external liquidity rather than focusing on changing ownership.
Vonoprazan
Authors: Provenza Delaney , Provenza John Michael
Published: November 2024

Helicobacter pylori is the most common chronic bacterial infection worldwide. Because of the risk for chronic gastritis, peptic ulcer disease, and gastric malignancy, all patients with H. pylori should be treated. Unfortunately, eradication rates remain low, and barriers to successful treatment include inadequate acid suppression, locoregional antibiotic resistance, and patient nonadherence to complicated treatment regimens. Vonoprazan, a new medication for the treatment of H. pylori infections, provides more potent acid suppression and is simpler to dose than proton pump inhibitors. This article provides a data-driven algorithm for incorporating vonoprazan into the treatment of patients with H. pylori infections.
Postoperative Opioid Consumption After Discharge: An Update From the Michigan Surgical Quality Collaborative Registry
Authors: Kulkarni Ashwin J. , Gunaseelan Vidhya , Brummett Chad M. , Waljee Jennifer , Englesbe Michael , Bicket Mark C.
Published: November 2024

Objective:

To evaluate opioid consumption for 21 procedures over 4 years from the Michigan Surgical Quality Collaborative (MSQC) registry and update post-discharge prescribing guidelines.

Background:

Opioids remain a common treatment for postoperative pain of moderate-to-severe intensity not adequately addressed by nonopioid analgesics, but excessive prescribing correlates with increased usage. This analysis provides updates and compares patient-reported consumption in response to new guidelines.

Methods:

We examined data from the MSQC registry for opioid-naive adult patients undergoing surgery between January 1, 2018, and October 31, 2021. The primary outcome was patient-reported opioid consumption in oxycodone 5 mg equivalents. Guidelines were anchored to the 75th percentile of consumption, updating previous guidelines from January 2020 based on data from January 1, 2018, to May 31, 2019.

Results:

39,493 opioid-naive surgical patients (average age 53.8 years [SD 16.4], 56.3% female, 19.1% non-White, 43.9% with public insurance) were included. Guidelines did not change for 7 of the 16 procedures including the most common procedures: minor hernia, laparoscopic cholecystectomy, laparoscopic appendectomy, and laparoscopic hysterectomy. Recommended prescribing ranges were lower for 9 procedures, with most (8) procedures having a reduction of 5 pills. Prescribing guidelines were developed for 5 new procedures. All procedures had upper-limit guidelines of 10 pills or less.

Conclusions:

For most procedures, patient-reported opioid consumption decreased between 2018 and 2021 when compared to the period between 2018 and 2019. New guidelines were established for a dozen procedures to balance maximizing pain control with reducing harms from inappropriate prescribing.
Heterogeneous Treatment Effects of High-Frequency Oscillatory Ventilation for Acute Respiratory Distress Syndrome: A Post Hoc Analysis of the Oscillation for Acute Respiratory Distress Syndrome Treated Early (OSCILLATE) Trial
Authors: Kobayashi Hirotada , Angriman Federico , Ferguson Niall D. , Adhikari Neill K. J.
Published: November 2024

OBJECTIVES:

We sought to evaluate whether different subgroups of adults with acute respiratory distress syndrome (ARDS) respond differently to high-frequency oscillatory ventilation (HFOV).

DESIGN:

The Oscillation for ARDS Treated Early (OSCILLATE) trial was a randomized controlled trial of HFOV vs. conventional ventilation that found an increased risk of in-hospital mortality (primary outcome) with HFOV. In a post hoc analysis, we applied three different approaches to evaluate heterogeneity of treatment effect for in-hospital mortality: 1) subgroup analyses based on baseline Pao
2:Fio
2 ratio and oxygenation index (OI); 2) a risk-based approach using a multivariable outcome prediction model; and 3) a clustering approach via multivariable latent class analysis. We used multivariable logistic regression models to assess for interaction.

SETTING:

Thirty-nine ICUs, five countries.

SUBJECTS:

Five hundred forty-eight adults with moderate to severe ARDS.

INTERVENTIONS:

HFOV vs. conventional mechanical ventilation with low tidal volume and higher positive end-expiratory pressure.

MEASUREMENTS AND MAIN RESULTS:

The effect of HFOV on in-hospital mortality was consistent across categories of Pao
2:Fio
2 ratio (adjusted odds ratio [aOR], 2.04; 95% CI, 1.32–3.17 and aOR, 1.16; 95% CI, 0.49–2.75 for groups with Pao
2:Fio
2 above or equal to 80, vs. below 80, respectively; interaction p = 0.23) and OI (aOR, 1.78; 95% CI, 0.67–4.70; aOR, 3.19; 95% CI, 1.44–7.09; aOR, 1.73; 95% CI, 0.82–3.65; and aOR, 1.33; 95% CI, 0.61–2.90 for quartiles of baseline OI, respectively; interaction p = 0.44). Point estimates for the effect of HFOV were consistent across risk categories (aOR, 2.44; 95% CI, 0.40–14.83; aOR, 1.69; 95% CI, 0.75–3.85; and aOR, 2.10; 95% CI, 0.59–7.54 for the lowest, moderate, and highest risk categories, respectively; interaction p = 0.32). Using a clustering approach, point estimates for HFOV were also consistent (cluster 1: aOR, 1.85; 95% CI, 1.15–3.00 and cluster 2: aOR, 1.75; 95% CI, 0.91–3.38; interaction p = 0.75).

CONCLUSIONS:

We did not identify heterogeneity in the effect of HFOV across different subgroups of patients with ARDS.
Comparison of associations between proximity to major roads and all-cause mortality across a spectrum of cardiovascular diseases
Authors: Raab Henry , Breen Miyuki , Weaver Anne M. , Moyer Joshua , Cascio Wayne E. , Diaz-Sanchez David , Ward-Caviness Cavin K.
Published: November 2024

Background:

Global urbanization is leading to increased exposure to traffic-related air pollution (TRAP), which is associated with adverse health events. While individuals with cardiovascular disease (CVD) are known to have elevated susceptibility to air pollution exposure, no studies have evaluated how mortality risks associated with TRAP exposure differ based on the presence of CVD.

Methods:

We used three electronic health record-based cohorts to examine associations between proximity to major roadways and all-cause mortality. The three cohorts were a random sample of the hospital population, individuals with a prior myocardial infarction, and individuals with diagnosed heart failure (HF). We used Cox proportional hazards models to evaluate associations while adjusting for age, race, sex, and census block group socioeconomic status.

Results:

Residing <250 m from a major roadway was associated with a hazard ratio (HR) of 1.13 (95% confidence interval = 1.05, 1.23) for individuals with HF, an HR of 1.07 (95% confidence interval = 0.96, 1.20) for those with a prior myocardial infarction, and an HR of 1.03 (95% confidence interval = 0.89, 1.20) for a random sample of hospital patients. This pattern persisted across several sensitivity analyses including alternative definitions of proximity to major roadways and matching the cohorts on demographics.

Conclusion:

These results highlight the differences in air quality-related health risks based on underlying CVD. Individuals with HF consistently had the highest environmental health risks. These results may better inform risks related to TRAP exposure in populations with differing underlying CVD.
Examining Whole Blood, Total and Free Plasma Tacrolimus in Elderly Kidney Transplant Recipients
Authors: Cossart Amelia R. , Isbel Nicole M. , Campbell Scott B. , McWhinney Brett , Staatz Christine E.
Published: November 2024

Background:

Therapeutic monitoring is routinely performed to ensure tacrolimus whole-blood concentrations fall within a predefined target. Despite this, patients still experience inefficacy and toxicity that could be related to variability in free (unbound) tacrolimus exposure. Therefore, the aim of this study was to compare tacrolimus-free plasma (Cu), total plasma (Cp), and whole-blood (Cwb) concentrations in adult kidney transplant recipients and to characterize tacrolimus disposition across different matrices.

Methods:

Twelve-hour concentration–time profiling was performed in 15 recipients, allowing simultaneous measurement of Cu, Cp, and Cwb. Pharmacokinetic parameters were estimated using noncompartmental analysis. The relationship between Cwb and Cp were examined using a capacity-limited binding model, incorporating the hematocrit fraction (f
HCT) to estimate maximum binding concentration (B
max) and dissociation constant (K

d
). The relationship between Cp and Cu was evaluated using a linear binding model to estimate the nonspecific binding parameter (N

plasma
). Nonlinear regression analysis was used to obtain estimates of B
max, K

d
, and N

plasma
.

Results:

A total of 195 paired Cwb, Cp, and Cu values were collected. The median ratios of Cwb:Cp, Cp:Cu, and Cwb:Cu were 9:1, 20:1, and 138:1, respectively. Variability in free plasma exposure was large; free trough values ranged from 8 to 51 ng/L and free area-under-the-concentration–time-curve values ranged from 424 to 7160 ng·h/L. Median (range) estimates of B
max, K

d
, and N

plasma
were 90.4 µg/L (22.4–752.5 µg/L), 2.36 µg/L (0–69.2 µg/L), and 0.05 (0.035–0.085), respectively. The interindividual variability (CV%) in binding parameters was considerable (B
max 117.2%; N

plasma
32.5%).

Conclusions:

Large variability was observed in tacrolimus-free plasma exposure and binding parameters. Future research to characterize the relationship between tacrolimus Cu and patient outcomes may be of benefit.
Hemodynamic effects of carvedilol plus simvastatin in cirrhosis with severe portal hypertension and suboptimal response to β-blockers: A double-blind, placebo-controlled, randomized trial
Authors: Alvarado-Tapias Edilmar , Brujats Anna , Puente Angela , Ardevol Alba , Rodriguez-Arias Ainhoa , Fajardo Javier , Pavel Oana , Garcia-Guix Marta , Aracil Carles , Poca Maria , Cuyàs Berta , Cantó Elisabet , Montañés Rosa , Garcia-Osuna Alvaro , Escorsell Àngels , Torras Xavier , Villanueva Càndid
Published: November 2024

Background and Aims:

Carvedilol is a nonselective β-blocker (NSBB) with anti-α1-adrenergic activity, more effective than traditional NSBBs in reducing portal pressure hepatic venous pressure gradient (HVPG). However, 35%–45% of patients still have insufficient HVPG decrease. Statins ameliorate endothelial dysfunction, reduce hepatic vascular resistance, and have pleiotropic effects. We investigated whether the addition of simvastatin improves the efficacy of carvedilol on HVPG in cirrhosis with severe portal hypertension and suboptimal response to traditional NSBBs.

Methods:

Patients with cirrhosis and high-risk varices referred for primary prophylaxis were consecutively included. HVPG was measured at baseline and again after i.v. propranolol. Suboptimal responders (HVPG decrease <20%) were treated with carvedilol and were randomized to double-blind administration of placebo or simvastatin. Chronic HVPG response was assessed after 4–6 weeks, repeating HVPG measurements after a standard liquid meal to estimate endothelial dysfunction. Plasma samples were obtained before each study to investigate inflammatory parameters.

Results:

Of 184 eligible patients, 82 were randomized to carvedilol + simvastatin (N = 41) or carvedilol + placebo (N = 41). Baseline characteristics were similar. HVPG significantly decreased with both, carvedilol + simvastatin (18.6 ± 4 to 15.7 ± 4 mm Hg, p < 0.001) and carvedilol + placebo (18.9 ± 3 to 16.9 ± 3 mm Hg, p < 0.001). The decrease was greater with carvedilol + simvastatin (2.97 ± 2.5 vs. 2.05 ± 1.6 mm Hg, p = 0.031). An HVPG decrease ≥20% occurred in 37% versus 15% of patients, respectively (OR: 3.37, 95% CI = 1.15–9.85; p = 0.021). With test meal, HVPG increased in both groups (p < 0.01), although carvedilol + simvastatin attenuated such increment (12 ± 8% vs. 23 ± 16%, p < 0.001). Cytokine levels (Interleukine-6, monocyte-chemoattractant protein-1, and malondialdehyde) decreased significantly more with carvedilol + simvastatin (p < 0.01). The incidence of adverse events was similar.

Conclusions:

In patients with severe portal hypertension (all with high-risk varices) and suboptimal hemodynamic response to traditional NSBBs, combined therapy with carvedilol plus simvastatin significantly enhances the portal pressure reduction achieved with carvedilol monotherapy, improves endothelial dysfunction, and reduces proinflammatory cytokines.
Operational Radiation Safety Considerations During Equine Superficial Radiation Treatment Using Portable X-Ray Devices
Authors: Singh Ashutosh , Johnson Thomas , Wotman Kathryn , Leary Del
Published: November 2024

Veterinary personnel exposure due to scattered x rays, when present during superficial radiation treatment (SRT), was evaluated. Veterinary personnel presence is needed during SRT to minimize the degree of required aesthesia to horses. Animal treatment was simulated, and exposure rates determined for 50, 70, and 100 kV x rays using eight different SRT applicators. Exposure rates at the surface of a solid water phantom (SWP) phantom ranged from 3.9 mR h−1 to 396 mR h−1 for 50 kV, from 41 mR h−1 to 2,880 mR h−1 for 70 kV, and from 235 mR h−1 to 7,500 mR h−1, for 100 kV, respectively. A horse phantom was used to mimic SRT equine ocular treatment creating a spatial exposure field where the directional scatter was measured at 1 m. The minimum distance away from the source to reach < 2 mR h−1 varied with angular position and energy and was lowest for all energies directly behind the x-ray tube. The closest distance before exceeding 2 mR h−1 at 50 kVp was determined to 1.96 m. A worker could stand 1 m behind the x-ray tube at 50 kVp with 0.25 mm lead for 15,106 hours. Typical SRT treatment times for horse eyelid squamous cell carcinoma are less than 5 minutes, and radiation doses to practitioners are expected to be well below local administrative ALARA limits.
Platelets and circulating (tumor) cells: partners in promoting metastatic cancer
Authors: Gautam Deepa , Clarke Emily M. , Roweth Harvey G. , Smith Margaret R. , Battinelli Elisabeth M.
Published: November 2024

Purpose of review

Despite being discovered decades ago, metastasis remains a formidable challenge in cancer treatment. During the intermediate phase of metastasis, tumor cells detach from primary tumor or metastatic sites and travel through the bloodstream and lymphatic system to distant tissues. These tumor cells in the circulation are known as circulating tumor cells (CTCs), and a higher number of CTCs has been linked to poor prognoses in various cancers. The blood is an inhospitable environment for any foreign cells, including CTCs, as they face numerous challenges, such as the shear stress within blood vessels and their interactions with blood and immune cells. However, the exact mechanisms by which CTCs survive the hostile conditions of the bloodstream remain enigmatic. Platelets have been studied for their interactions with tumor cells, promoting their survival, growth, and metastasis. This review explores the latest clinical methods for enumerating CTCs, recent findings on platelet-CTC crosstalk, and current research on antiplatelet therapy as a potential strategy to inhibit metastasis, offering new therapeutic insights.

Recent findings

Laboratory and clinical data have provided insights into the role of platelets in promoting CTC survival, while clinical advancements in CTC enumeration offer improved prognostic tools.

CTCs play a critical role in metastasis, and their interactions with platelets aid their survival in the hostile environment of the bloodstream. Understanding this crosstalk offers insights into potential therapeutic strategies, including antiplatelet therapy, to inhibit metastasis and improve cancer treatment outcomes.
An unexpected cause of intractable dysphagia after 20 years following cervical spine instrumentation using bone cement alone: a case report
Authors: Bohara Sandeep , Thapa Bikas , Regmi Prakash , Shilpakar Sushil K.
Published: November 2024

Introduction and Importance:

Postoperative dysphagia following anterior cervical discectomy fusion (ACDF) for cervical disc herniation is still poorly understood. Dysphagia after anterior spinal cervical approach is mild and transient. Here, the authors present a rare case suffering with severe progressive dysphagia for over 1 year after 20 years of ACDF due to expulsed bone cement abutting the esophagus which was successfully removed after reoperation.

Case Presentation:

A 59-year-old homemaker female presented to us with a foreign body sensation in the throat ‘globus pharyngeus’ and progressive difficulty in swallowing for 1 year. She was previously operated for C5-C6 cervical intervertebral disc prolapse via ACDF using bone cement at another center. On examination, power in the left upper limb was MRC grade 3, and the left-hand grip was 25% only. MRI of the cervical spine showed increased prevertebral soft tissue space and a notable rectangular-shaped black prevertebral shadow at the C5-C6 level, causing esophageal compression. The patient underwent an exploration of previous ACDF surgery. Intraoperative findings revealed an extruded piece of bone cement of size ~2×1.5×1 cm3 at C5-C6 disc space level, compressing the esophagus. The yellowish extruded piece was removed and C5-C6 was reinforced with an anterior cervical plate with screws. The postoperative course was uneventful.

Clinical Discussion:

The exact pathophysiology of dysphagia after ACF surgery remains unknown. In our case, there was an expulsion of the graft. The graft used was polymethyl methacrylate, commonly known as bone cement, which was placed 20 years back. Since polymethyl methacrylate is bioinert material, the graft may have expulsed from its site of placement and thus compressed the esophagus. Taking into consideration of the cost-effectiveness and maintenance of spinal mobility, few neurosurgeons believe that the application of bone cement in ACF surgery as a spacer is a safe and very cost-effective modality compared to modern expensive artificial disc.

Conclusion:

Dysphagia after ACDF surgery is usually underrecognized. Although the serious complications after ACDF surgery are rare, dysphagia can cause prolonged morbidity to patients. Using bone cement alone for ACDF surgery may carry the risk of its anterior expulsion even after a long period of surgery.
Prenatal Diagnosis and Management of Generalized Arterial Calcification of Infancy
Authors: Kuppuswami Narmadha , Vijayaraghavan Boopathy
Published: November 2024

BACKGROUND:

Generalized arterial calcification of infancy is a rare genetic disorder that was first reported in 1899. Since then, slightly more than 200 cases have been documented. This rare autosomal recessive disorder occurs when the homozygous ENPP1 gene mutation is associated with abnormal calcification in the medium and large arteries in the fetus. Overall mortality in individuals with generalized arterial calcification of infancy is high (55%) before the age of 6 months, with 24.4% dying in utero. Due to the high mortality rate, there is a critical need for additional reports and research regarding generalized arterial calcification of infancy.

CASE:

We submit a case report of a child with generalized arterial calcification of infancy—a unique instance in which the diagnosis was established prenatally and treatment was initiated in utero. Patient care was continued through a multidisciplinary approach coordinated between specialists across India, Australia, and the United States. There was an almost complete resolution of the calcification, with near-normal development and intellectual capacity of the child for age.

CONCLUSION:

Clear guidelines are needed regarding prenatal use of bisphosphonate therapy, timing, dosage, and duration of treatment for fetuses with ENPP1 gene mutations to minimize disease progression and improve neonatal health at birth. This case further illustrates how involving well-informed parents in decision making can help tailor the appropriate treatment. Our report also describes the possibility of new, ongoing clinical trials that may pave the way for a cure for this child and others.
Immunohistochemistry in the Differential Diagnosis of Triple Negative Breast Carcinoma and High-grade Serous Carcinoma: Old and New Markers
Authors: Jain Pragya Virendrakumar , Molina Mariel , Moh Michelle , Bishop Erin , Rader Janet S. , Jorns Julie M.
Published: November 2024

Distinction of metastasis to the breast from a breast primary, particularly high-grade triple-negative breast cancer (TNBC), can be challenging due to nonspecific morphology and immunohistochemical (IHC) profiles. Among metastases to the breast, high-grade serous carcinoma (HGSC) of müllerian origin is most likely to be misdiagnosed as TNBC. We assessed breast and müllerian markers on TNBC and HGSC, including keratin 7, keratin 20, GATA3, GCDFP15, mammaglobin, p53, PAX8 (MRQ50 and BC12 clones), TRPS1, SOX10, and WT1. Of 151 TNBC cases, TRPS1 had the highest sensitivity, showing expression in 149 (98.7%) cases, followed by SOX10 (110/151; 72.8%), GATA3 (102/151; 67.5%), GCDFP15 (29/151; 19.2%), and mammaglobin (27/151; 17.9%). PAX8 positivity was seen in 40.4% (61/151) of TNBC via the MRQ50 clone but was negative in all via the BC12 clone. Of 185 HGSC cases, PAX8 via the MRQ50 clone was the most sensitive (179/185; 96.8%), followed by WT1 (171/185; 92.4%) and PAX8 via the BC12 clone (164/185; 88.6%). In addition, TRPS1 positivity was seen in 75 HGSC cases (40.5%). Aberrant p53 patterns were seen in 64.9% (98/151) of TNBC and 94.1% (174/185) of HGSC. TRPS1 positivity in HGSC and PAX8 positivity via the MRQ50 clone in TNBC represent potential pitfalls in assessing high-grade carcinoma for which the differential diagnosis includes TNBC and HGSC. However, with this knowledge, utilization of a panel of breast and müllerian markers, including preferential use of the PAX8 BC12 clone, can facilitate accurate diagnosis.
Abbe Flap for Upper Lip Reconstruction
Authors: Giugliano Carlos , Echenique Patricia
Published: November 2024

Introduction:

Lips are complex structures that are part of the facial esthetics. Their integrity may be affected by congenital diseases, trauma, burns, and cancers, among other pathologies. The reconstruction of the upper lip subunit can be a challenge for the surgeon. The purpose of this paper is to review the Abbe flap technique with the help of tips from the primary surgeon (surgical tips) and present a series of cases as experience in upper lip reconstruction.

Methods:

A retrospective study at Chilean centers Fundación Gantz and Clínica Alemana de Santiago from 2003 to 2023. The surgical technique was described, and different variables were assessed. The Strasser scale was used as an objective method for assessing the results.

Results:

Sixteen surgery patients, 50% female and 50% male. Fourteen patients (87.5%) with cleft lip and palate. In total, 85.71% of the total number of patients with follow-up had a good score of 1 to 4 on the Strasser scale. There were no mediocre results comparable to results described in other series. There were no complications relating to the technique.

Conclusions:

The Abbe flap technique continues to be an excellent option in upper lip reconstruction, especially in patients with a condition of the middle third of the lip. Knowledge of the anatomy, the surgical technique, the function of the lip, and facial esthetics leads to acceptable results for the patient and their environment with this technique.
Speech Aid Prostheses For Patients With Cleft and Other Craniofacial Birth Conditions
Authors: Reisberg David J.
Published: November 2024

Normal speech production is a complex mechanism requiring the coordination of several organs of the oral cavity. The lip, hard and soft palates, and teeth all play a role in normal speech production. In cases of craniofacial birth conditions such as cleft lip and palate or ectodermal dysplasia, one or more of these areas may be compromised. Surgical correction is the most ideal means to provide normalcy but surgery may not always be appropriate or possible. In such cases, a speech aid prosthesis may serve as an interim or definitive way to normalize speech. This article describes the several options that may be employed toward this end.
Protective Strategies for Pituitary Function During Endoscopic Transnasal Pituitary Adenoma Surgery: A Single-center Experience
Authors: Yang Jihu , Zhang Fengmin , Chen Sihao , Zhang Xiejun , Liu Yufei , Zheng Wenjian , Chen Fanfan , Chen Lei , Huang Guodong
Published: November 2024

Objective:

This study investigated the impact of endoscopic transnasal pituitary adenoidectomy on function and discussed the factors that contribute to postoperative pituitary function. To provide a foundation for protecting pituitary function and improving the curative effect of pituitary adenoma neuroendoscope resection.

Methods:

From January 2019 to January 2022, in the Neurosurgery Pituitary Tumor Diagnosis and Treatment Research Center, the First Affiliated Hospital of Shenzhen University, the clinical data of 306 patients who underwent endoscopic transnasal pituitary adenoma surgery were analyzed retrospectively. The surgical treatment strategy was discussed and explored, while the factors related to pituitary function were examined based on tumor size and Knosp grade.

Results:

There were 40 cases (67.8%) of pituitary-thyroid axis, 18 cases (60%) of pituitary-adrenal axis, 25 cases (45.4%) of pituitary-gonad axis, 5 cases (62.5%) of pituitary-growth hormone axis, and 8 cases (72.7%) of diabetes insipidus with postoperative improves of hypopituitarism. Postoperative newly developed hypopituitarism occurred in 20 cases (8.1%) of pituitary-thyroid axis, 15 cases (5.4%) of pituitary-adrenal axis, 10 cases (4.0%) of pituitary-gonad axis, 5 cases (1.7%) of pituitary-growth hormone axis, and 8 cases (2.7%) of new diabetes insipidus. The incidence of pituitary-adrenal axis hypofunction in giant pituitary adenomas was significantly higher than that in microadenomas and macroadenomas (P<0.05). The incidence of hypopituitarism of Knosp grade 4 pituitary adenoma before operation was higher than that of other groups (P<0.05), but there was no significant difference in the incidence of new hypopituitarism after operation (P>0.05).

Conclusions:

In endoscopic transnasal pituitary adenoma surgery, the incidence of hypothyroidism and adrenal gland dysfunction is higher than in other hormone axes, but the recovery rate is also higher, and the recovery rate of sex hormones is lower. The incidence of postoperative hypothyroidism increases dramatically with tumor size and tumor invasiveness.
Local Flaps for Concomitant Reconstruction of 3 Adjacent Forehead Defects: Is It Feasible?
Authors: Seretis Konstantinos , Bounas Nikolaos , Xergia Vasiliki , Vergidou Afroditi
Published: November 2024

The cornerstones of forehead reconstruction are the provision of adequate skin paired with a satisfactory cosmetic outcome without hairline and eyebrows distortion. Several techniques have been described over the years to reconstruct sizable defects. Currently, an individualized approach, based on the patient’s medical status and needs, the defect characteristics, and the local tissue quality and availability, should be considered for an optimal outcome. This case exemplifies the reliability of local flaps’ combination to reconstruct concurrently 3 adjacent forehead defects, should innovative thinking and adequate planning be applied.
EXOSOMES FROM CYCLIC MICE MODULATE LIVER TRANSCRIPTOME IN ESTROUPAUSE MICE INDEPENDENT OF AGE
Authors: Zanini Bianka M. , Ávila Bianca M. , Hense Jéssica D. , Garcia Driele N. , Ashiqueali Sarah , Alves Pâmela I. C. , Oliveira Thais L. , Collares Tiago V. , Brieño-Enríquez Miguel A. , Mason Jeffrey B. , Masternak Michal M. , Schneider Augusto
Published: November 2024

Background

Exosomes are extracellular vesicles secreted by cells that contain microRNAs (miRNAs). These miRNAs can induce changes in gene expression and function of recipient cells. In different cells exosome content can change with age and physiological state affecting tissues function and health.

Aims

Therefore, the aim of this study was to characterize the miRNA content and role of exosomes from cyclic female mice in the modulation of liver transcriptome in estropausal mice.

Main Methods

Two-month-old female mice were induced to estropause using 4-vinylcyclohexene diepoxide (VCD). At six months of age VCD-treated mice were divided in control group (VCD) and exosome treated group (VCD+EXO), which received 10 injections at 3-day intervals of exosomes extracted from serum of cyclic female mice (CTL).

Key findings

Exosome injection in estropausal mice had no effect on body mass, insulin sensitivity or organ weight. We observed ten miRNAs differentially regulated in serum exosomes of VCD compared to CTL mice. In the liver we observed 931 genes differentially expressed in VCD+EXO compared to VCD mice. Interestingly, eight pathways were up-regulated in liver by VCD treatment and down-regulated by exosome treatment, indicating that exosomes from cyclic mice can reverse changes promoted by estropause in liver.Cyp4a12aexpression which is male-specific was increased in VCD females and not reversed by exosome treatment.

Significance

Our findings indicate that miRNAs content in exosomes is regulated by estropause in mice independent of age. Additionally, treatment of estropausal mice with exosomes from cyclic mice can partially reverse changes in liver transcriptome.
Actin turnover and myosin contractility determine emergent Thickness Robustness of Cell-Mimicking Cortex
Authors: Gat S. , Amit Y. , Livne G. , Sanchez Daniel Sevilla , Porat N. , Yochelis A. , Gov N.S. , Bernheim-Groswasser A.
Published: November 2024

Cell shape deformation is primarily determined by the actin cortex, a thin network of actin filaments and myosin motors, that lies beneath and attached to the plasma membrane of cells and endows cells with their mechanical stability and structural integrity. Since inside the cells there are hundreds of proteins associated with the actin cortex, it is very difficult to identify the role of each component and the mechanisms that maintain a functional cortex. Here, using a minimal set of components we recreate dynamic treadmilling in an actomyosin cortex on a bilayer membrane with cell-mimicking characteristics, in the absence and presence of myosin-II molecular motors. We reveal how treadmilling is regulated by actin network disassembly factors and myosin contractility, and how this drives the robustness of the cortical thickness to concentration fluctuations in cytoskeletal components.

One-Sentence Summary

Recreating the cellular skeleton network that determines cell shape and integrity using a minimal set of cellular building-blocks.
pH-dependent structural dynamics of the neuropeptide Y in aqueous solution
Authors: Nguyen Thi Hoa , Spehr Marc , Ana-Nicoleta  , Carloni Paolo
Published: November 2024

Neuropeptide Y regulates key molecular processes in the brain. Its interaction with the cell membrane, fundamental for its function, is likely pH-dependent. Here, we perform constant pH simulations on the peptide in solution to investigate the impact of acidification on its protonation states and on its intra-molecular H-bond network. Our simulations point to a quite complex scenario at neutral or mildly acidic pH, where ionizable residues such as Asp, Glu, and His may exhibit fractional protonation states, affecting the conformational dynamics of the peptide in a non-trivial manner. Unanticipated structural dynamics emerge at low pH, where carboxyl groups are all neutral and histidine is di-protonated. Moreover, changes in protonation influence intra-molecular hydrogen bonding. Thus, using constant pH simulations could prove important to describe the structural peptide / protein dynamics at pH values that deviate from neutral.
Structuring Role of Tau-Tubulin Co-Condensates in Early Microtubule Organization
Authors: Lee-Eom Chaelin , Jung Jaehun , Park Celine , Shon Min Ju
Published: November 2024

Tau protein, a key microtubule-associated protein in neurons, is traditionally known for stabilizing microtubules. However, its recently discovered ability to undergo liquid-liquid phase separation (LLPS) reveals a broader, dynamic role in nucleating and organizing microtubule networks. Here, using a combination of real-time imaging and a geometric approach based on Voronoi tessellation, we examined how tau condensation leads to clustering and local tubulin enrichment, supporting microtubule organization. Our observations show that tau-tubulin co-condensates not only initiate nucleation and branching of microtubules but also drive the network’s gradual evolution through a “dynamic weaving” process. By generating Voronoi diagrams from super-resolution and confocal microscopy images of the stabilized network, we quantitatively mapped tubulin enrichment as a function of tau density, revealing that high-density tau clusters, approximately 0.2 μm in size, correlate with tubulin-rich spots at equilibrium. Overall, these findings provide new insights into tau-tubulin co-condensates as dynamic structuring elements, whose liquid-like properties continuously reshape the microtubule network, creating a flexible and adaptive architecture essential for cellular function.
Development, evaluation, and implementation of a tablet device-based depression screening and management tool for rural womens self-help groups
Authors: Kalidindi Bharat , Waghmare Abijeet , Krishnamachari Srinivasan , Pradeep Johnson , Goud Ramakrishna B , Bhat Amritha , Devadass Dhinagaran , Raj Tony D S
Published: November 2024

Depression is a critical public health issue among women in rural India, with diagnosis and treatment rates being very low. The paper summarizes the development of MITHRA, a user-centred mobile app for depression screening and treatment among women in self-help groups (SHGs) of rural India. The predevelopment phase involved situation analysis and forming participatory design groups of prospective users. The app development phase used an Agile approach for flexibility and rapid adaptation. The post-development phase involved user acceptance testing, training on app usage, data synchronization, accuracy testing and usability evaluation. The study found that only 25% of the women in the participatory design group were digitally literate, despite 63% smartphone ownership. On assessing the cellular connectivity, the average download speed across the eight study sites was 9.81 Mbps, and the average upload speed was 4.6 Mbps. The user tests showed improvement in the task success rate between user testing session 1 and session 2 for all the tested tasks. The app successfully passed user acceptance testing (UAT) and data accuracy testing, demonstrating its readiness for deployment. Heuristic evaluation identified 52 violations with a mean score of 2.3, indicating minor usability issues to be addressed. This description of app development underscores the potential of mHealth apps in addressing mental health issues in underrepresented populations.
Hamstring strain grade on MRI and return to play in elite Australian cricket players
Authors: Cooney Thomas , Reeve Ashton , Saw Anna E. , Kountouris Alex , Orchard John W. , Linklater James
Published: November 2024

Objective

i) determine whether the grade of hamstring strain confirmed by magnetic resonance imaging (MRI) is related to time to return to play, and ii) describe the incidence, prevalence and grade of hamstring strains confirmed by MRI in elite Australian cricket players.

Design

Retrospective case series.

Methods

Hamstring strains from professional domestic and international cricket teams over 13.5 seasons which had received MRI scans were graded using British Athletics Muscle Injury Classification (BAMIC) system. The main outcome measure was time to return to play.

Results

141 hamstring strain injuries with available MRI imaging scans were recorded during the study period (average 3.2 per 100 players per season: male 4.5, female 1.2). The most commonly injured muscle was biceps femoris (64%, 95% CI 56-71%) and the most frequent category of injury was grade 2C (27%, 20-35%). Across all injury grades, players were unavailable for full participation for a median of 23 (IQR 15-38) days and missed 3 (1-6) matches. The number of days unavailable were higher for injuries which were graded 2 or 3, compared to grade 1 (p=0.018, p=0.002 respectively), and injuries which included the tendon compared to those which did not (p=0.002).

Conclusions

This study provides evidence that higher grade injuries and those involving the intramuscular tendon are associated with a more prolonged return to play. This finding should be viewed in context of the study limitation that clinicians treating players were not blinded to the MRI findings.
Genetics and biology of pancreatic ductal adenocarcinoma
Authors: Ying Haoqiang , Kimmelman Alec C. , Bardeesy Nabeel , Kalluri Raghu , Maitra Anirban , DePinho Ronald A.
Published: November 2024

Pancreatic ductal adenocarcinoma (PDAC) poses a grim prognosis for patients. Recent multidisciplinary research efforts have provided critical insights into its genetics and tumor biology, creating the foundation for rational development of targeted and immune therapies. Here, we review the PDAC genomic landscape and the role of specific oncogenic events in tumor initiation and progression, as well as their contributions to shaping its tumor biology. We further summarize and synthesize breakthroughs in single-cell and metabolic profiling technologies that have illuminated the complex cellular composition and heterotypic interactions of the PDAC tumor microenvironment, with an emphasis on metabolic cross-talk across cancer and stromal cells that sustains anabolic growth and suppresses tumor immunity. These conceptual advances have generated novel immunotherapy regimens, particularly cancer vaccines, which are now in clinical testing. We also highlight the advent of KRAS targeted therapy, a milestone advance that has transformed treatment paradigms and offers a platform for combined immunotherapy and targeted strategies. This review provides a perspective summarizing current scientific and therapeutic challenges as well as practice-changing opportunities for the PDAC field at this major inflection point.