bluuebunny/crossref_metadata_2025 huggingface dataset:
Insights into atypical segmental layer thicknesses and phase retardation in thick corneas using ultrahigh-resolution polarization-sensitive optical coherence tomography
Authors: Patil Rahul P. , Shetty Rohit , Khamar Pooja , Patel Yash G. , Narasimhan Raghav R. , Bhatkal Anushree A. , Hitzenberger Christopher K. , Pircher Michael , Nuijts Rudy M. M. R. , Sinha Roy Abhijit
Published: July 2024

Background

Accurately assessing corneal structural status is challenging when thickness deviates from the average. Polarization-sensitive optical coherence tomography (PS-OCT) measures tissue-specific polarization changes, providing additional contrast for accurate segmentations and aids in phase retardation (PR) measurements. Previous studies have shown PR's effectiveness in identifying sub-clinical keratoconus (KC) in asymmetric cases. Thus, this study aims to assess PR distribution in thick corneas with and without KC.

Methods

In this retrospective and cross-sectional study, 45 thick corneas from 30 Asian-Indian subjects, categorized into healthy (n = 26) and KC (n = 19) groups were analyzed. All eyes underwent standard clinical evaluations, tomographic assessments, and corneal biomechanics measurements. PR and individual layer thicknesses were measured using custom-designed ultrahigh-resolution PS-OCT. PR en-face maps were generated. Individual layer thicknesses and PR analysis was conducted across multiple zones, extending up to 8–10 mm in diameter. All eyes in the study had not undergone interventions, received topical medications, or had previous corneal disease history.

Results

Significant differences were found in spherical and cylindrical powers, keratometry, pachymetry, and biomechanical indices (all P < 0.01). Thickness profiles from PS-OCT showed significant differences in the 4–8 mm zones only. Bowman's layer thickness significantly differed only in the central 2 mm zone (P = 0.02). The median PR values showed marginal differences in the central 2 mm zone (P = 0.0565). Additionally, there were significant differences observed in the 2–4 mm and 4–6 mm zones (P = 0.0274 and P = 0.0456, respectively). KC eyes exhibited an atypical PR distribution and corneal thinning, while normal eyes maintained a uniform Bowman’s layer thickness and PR maps with larger areas of higher PR.

Conclusion

The study revealed distinctive PR distribution in thick corneas among healthy and KC groups. Using an ultrahigh-resolution PS-OCT the significance of Bowman's layer thickness in these groups was also emphasized. The study offered potential improvements in clinical diagnostics by enhancing our understanding of corneal structure and its altered function.
Comparative efficacy of citric acid/tartaric acid/malic acid additive-based polyvinyl alcohol-starch composite films
Authors: Das Aritra , Saha Muktashree , Gupta Manish Kumar , Rangan Latha , Uppaluri Ramagopal , Das Chandan
Published: July 2024

To ascertain upon the ideal configuration of physico-mechanical qualities, efficient processing techniques, and network stability of the prepared bio-composite films in real-world applications, the polymeric materials shall be subjected to a careful manipulation. Such bio-composite films have outstanding combinations of biocompatibility and toxicity-associated safety qualities. Such research interventions will be beneficial for the packaging, pharmaceutical, and biomedical industries that wish to target and adopt them for commercial applications. In this article, three alternate organic acids, i.e., citric acid (CA), tartaric acid (TA), and malic acid (MA), are blended separately into polyvinyl alcohol (PVA)-starch (St)-glycerol (Gl) composite films and for the targeted purpose of enhanced crosslinking, plasticizing, and antibacterial capability of the polymer network. The organic acid-based bio-composite polymeric films were assessed in terms of swelling index (SI), in vitro degradation, tensile strength (TS), percentage elongation (%E), antibacterial activity, and cytotoxicity attributes. Among these, the MA-based PVA composite films outperformed the CA-based PVA composite film in terms of absorbency (SI 739.29%), mechanical strength (TS 4.88 MPa), and elasticity (%E 103.68%). Furthermore, following a 24-h incubation period, the MA-based films exhibited the highest proliferative effect of 215.59% for the HEK cells. In conclusion, the MA has been inferred to be the most relevant organic acid for the desired optimality of film composition, physical and biological properties, and cost.
Dynamic home range of the grey-sided vole Craseomys rufocanus: a pilot study
Authors: Frafjord Karl
Published: July 2024

Background

Knowledge about home range size is vital to understand social systems and population dynamics of small mammals, as well as dispersal and a species’ landscape use. Home ranges have been mapped for some species of voles (subfamily Microtinae) but remain virtually unknown for many species, including the grey-sided vole Craseomys rufocanus.

Results

A small pilot study was carried out in an inland valley of northern Norway, where six adult C. rufocanus were radio-tracked with one male and one female in each of the summers 2021–2023. Despite the small sample size, a large variation in home range size was found; males 2 294 − 36 887 m2 and females 1 728-7 392 m2 (100% MCP). Three of the voles tracked over a prolonged period of time showed a dynamic use and shifting of the range. Home range size and use was mostly related to reproduction. The male with the smallest range had probably not yet become reproductively active, whereas the male with the largest range was searching for females at a time when vole density was very low. The third male reduced his range when the reproductive season ended. For females the most important limitations were food, shelter and dependent young, those with young needed to return frequently and spend more time at the nest site. When the reproductive season ended, one female increased her range, perhaps exploring sites to overwinter.

Conclusions

Home range use in this population appears to be more dynamic than has previously been reported for C. rufocanus. The large ranges of males most likely resulted from the search of reproductively active females, outside of the reproductive season male ranges approximated female ranges. Female ranges most likely were limited by the need to feed close to their nest with dependent young, being able to roam more freely when reproduction ended.
Proteins from shrews’ venom glands play a role in gland functioning and venom production
Authors: Kowalski Krzysztof , Marciniak Paweł , Nekaris K. Anne-Isola , Rychlik Leszek
Published: July 2024

Venom production has evolved independently many times in the animal kingdom, although it is rare among mammals. Venomous shrews produce venom in their submandibular salivary glands and use it for food acquisition. Only a few toxins have been identified in shrew venoms thus far, and their modes of action require investigation. The biological and molecular processes relating to venom production and gland functioning also remain unknown. To address this gap, we investigated protein content in extracts from venom glands of two shrew species, Neomys fodiens and Sorex araneus, and interpreted their biological functions. Applying a proteomic approach coupled with Gene Ontology enrichment analysis, we identified 313 and 187 putative proteins in venom glands of N. fodiens and S. araneus, respectively. A search of the UniProt database revealed that most of the proteins found in both shrew species were involved in metabolic processes and stress response, while GO enrichment analysis revealed more stress-related proteins in the glands of S. araneus. Molecules that regulate molecule synthesis, cell cycles, and cell divisions are necessary to enable venom regeneration and ensure its effectiveness in predation and food hoarding. The presence of proteins involved in stress response may be the result of shrews’ high metabolic rate and the costs of venom replenishment. Some proteins are likely to promote toxin spreading during envenomation and, due to their proteolytic action, reinforce venom toxicity. Finally, finding numerous proteins involved in immune response suggests a potential role of shrew venom gland secretions in protection against pathogens. These findings open up new perspectives for studying biological functions of molecules from shrew venom glands and extend our knowledge on the functioning of eulipotyphlan venom systems. Because the majority of existing and putative venomous mammals use oral venom systems to inject venom into target species, the methods presented here provide a promising avenue for confirming or discovering new taxa of venomous mammals.
Examining the impact of multimodal task design on English oral communicative competence in fourth-grade content-language integrated social studies: A quasi-experimental study
Authors: Lai Cheng-Ji
Published: July 2024

Content and Language Integrated Learning (CLIL) is increasingly adopted globally, including in Taiwan’s educational initiatives, yet challenges remain in implementing effective CLIL practices, such as pedagogy and curriculum design. This study investigated the effectiveness of multimodal task designs, combining hands-on learning with poster presentations, in enhancing oral communicative competence within CLIL contexts. Employing a mixed-methods, quasi-experimental design with a comparative case study framework, the study assessed English oral communicative competence in four intact fourth-grade Taiwanese CLIL Social Studies classes. The hands-on learning group (EG, n = 40) engaged in activities like Chinese Dumpling Making, Bird’s Nest Building, and Succulent Pot Designing, while the non-hands-on learning group (CG, n = 34) used traditional worksheets on the same topics. Both groups proceeded to poster presentations within their multimodal task design, where students’ oral communicative competence was assessed using rubrics developed based on Coyle’s 4Cs dimensions, focusing on Content, Communication, and Cognition. Additionally, students’ cultural knowledge related to the hands-on topics was evaluated through written tests. To complement the quantitative data, qualitative data from self-reported reflections and video recordings documenting interventions were collected for the assessment of oral communicative competence within a CLIL framework. Results demonstrate that integrating hands-on activities significantly enhanced procedural content, communication (i.e., sentence complexity, pronunciation accuracy for target vocabulary, presentation fluency), and cognitive abilities, confirming the efficacy of multimodal learning approaches in fostering linguistic and cognitive engagement. Post-test comparisons show the EG’s superiority in cultural knowledge acquisition across all three hands-on topics. Student reflections endorsed the enrichment of learning experiences through multimodal task design. Video analysis of both groups’ interventions revealed that despite significant engagement and autonomy, EG students commonly utilized general English rather than target vocabulary, a pattern similar to that observed in the CG. These findings highlight the potential of diverse modalities in CLIL to enhance English content learning and oral skills, shaping future pedagogy and language strategies in Taiwan. The study also emphasizes the role of embodied learning, the interplay between physical actions and cognitive processes, to facilitate deeper understanding and engagement with subject matter within CLIL settings.
Preclinical evaluation of CXCR4 peptides for targeted radionuclide therapy in glioblastoma
Authors: Waked Anthony , Crabbé Melissa , Neirinckx Virginie , Pérez Sunay Rodriguez , Wellens Jasmien , Rogister Bernard , Benotmane M. Abderrafi , Vermeulen Koen
Published: July 2024

Background

Glioblastoma (GBM), is the most fatal form of brain cancer, with a high tendency for recurrence despite combined treatments including surgery, radiotherapy, and chemotherapy with temozolomide. The C-X-C chemokine receptor 4 (CXCR4) plays an important role in tumour radioresistance and recurrence, and is considered as an interesting GBM target. TRT holds untapped potential for GBM treatment, with CXCR4-TRT being a promising strategy for recurrent GBM treatment. Our study focuses on the preclinical assessment of different 177Lu-labelled CXCR4-targeting peptides, CTCE-9908, DV1-K-DV3, and POL3026 for GBM treatment and exploring some of the radiobiological mechanisms underlying these therapies.

Results

All three DOTA-conjugated peptides could be radiolabelled with 177Lu with > 95% radiochemical yield. Binding studies show high specific binding of [177Lu]Lu-DOTA-POL3026 to U87-CXCR4 + cells, with 42% of the added activity binding to the membrane at 1 nM, and 6.5% internalised into the cells. In the presence of the heterologous CXCR4 blocking agent, AMD11070, membrane binding was reduced by 95%, a result confirmed by quantitative in vitro autoradiography of orthotopic GBM xenograft sections. An activity-dependent decrease in cell viability was observed for [177Lu]Lu-DOTA-DV1-K-DV3 and [177Lu]Lu-DOTA-POL3026, along with a slight increase in the induction of apoptotic markers. Additionally, the expression of γH2AX increased in a time-and activity-dependent manner. Ex vivo biodistribution studies with [177Lu]Lu-DOTA-POL3026 show uptake in the tumour reaching a SUV of 1.9 at 24 h post-injection, with higher uptake in the kidneys, lungs, spleen, and liver. Dosimetry estimations show an absorbed dose of 0.93 Gy/MBq in the tumour. A blocking study with AMD11070 showed a 38% reduction in tumour uptake, with no significant reduction observed in µSPECT imaging. Although no brain uptake was observed in the ex vivo biodistribution study, autoradiography on U87-CXCR4 + tumour inoculated mouse brain slices shows non-specific binding in the brain, next to high specific binding to the tumour.

Conclusions

In conclusion, we compared different 177Lu-radiolabelled CXCR4-targeting peptides for their binding potential in GBM, and demonstrated their varied cytotoxic action against GBM cells in vitro, with POL3026 being the most promising, causing considerable DNA damage. Though the peptide’s systemic biodistribution remains to be improved, our data demonstrate the potential of [177Lu]Lu-DOTA-POL3026 for CXCR4-TRT in the context of GBM.
Comprehensive nontargeted analysis of fluorosurfactant byproducts and reaction products in wastewater from semiconductor manufacturing
Authors: Chen Yi-Ju , Yang Jheng-Sian , Lin Angela Yu-Chen
Published: July 2024

Semiconductor manufacturing employs per- and polyfluoroalkyl substances (PFAS) as fluoroasurfactants to enhance the quality of photolithography lines. Our research, employing a fragment-based approach to investigate nontarget PFAS, overcomes conventional homologous series limitations. In a mixture of PFAS standards used as a quality control sample, 92% (36 out of 39 compounds spanning 11 compound classes) were detectable through the fragment-based nontarget procedure. This indicates the effectiveness of this approach in identifying the hydrophobic and hydrophilic characteristics of various fluorosurfactants. Eighty-three PFAS were detected in wastewater and effluent samples from semiconductor industry, including 29 newly discovered compounds, categorized into three groups. First, besides detecting perfluorobutane sulfonamido ethanol (FBSE), various fluoroalkyl chain structures of FBSE derivatives were initially identified in wastewater. These include perfluorobutyl ether sulfonamido ethanol, unsaturated FBSE, and hydrogen-substituted FBSE. These derivatives were also detected in trace amounts in commercial authentic standards of FBSE. To quantify their presence, we analyzed the FBSE derivatives from the authentic standard, and the relative proportions of these derivatives contribute to approximately 0.5%. This suggests that the FBSE derivative series detected in wastewater may arise from byproducts of chemical formulations used in the manufacturing of semiconductors. Second, transformation products from FBSE during oxidation, including the first identified intermediate transformation compounds, perfluorobutane sulfonamido acetaldehyde and its hydrate, were discovered. Third, diverse reaction products are generated from the intricate processes of semiconductor manufacturing, which utilize strong acids, bases, and solvents under UV light or heated conditions. These processes include the formation of PFAS-related compounds through hydration, sulfonation, oxidation, and nitrification. This study revealed 25 isomeric PFAS, encompassing headgroup isomers and functional tail group isomers. These findings underscore the importance of comprehending diverse reactions and the overall emission compositions of PFAS in semiconductor wastewater, highlighting its complexity and presenting challenges for subsequent wastewater treatment.
ACTH-producing adrenocortical carcinoma: an exceedingly rare diagnosis
Authors: Saraiva Miguel , da Inez Correia Raquel , Azevedo Sérgio Xavier , Brandão José Ricardo , Oliveira José Carlos , Palma Isabel
Published: July 2024

Background

Adrenocortical carcinoma is a very rare endocrinopathy that has a poor prognosis and is frequently associated with ACTH-independent Cushing’s syndrome. Despite having an adrenocortical carcinoma, our patient surprisingly had an ACTH-dependent Cushing’s syndrome.

Case report.

A 26-year-old female presented with Cushing’s syndrome and an abdominal mass. Imaging studies revealed an adrenal mass consistent with a high-grade malignancy. Laboratory workup showed hypercortisolism, hyperandrogenism, and hypokalemia with normal levels of metanephrines. Unexpectedly, her ACTH levels were remarkably elevated. The pathological analysis of a tumor sample was conclusive for adrenocortical carcinoma with immunopositivity for ACTH.

Conclusions

Our patient suffered from an adrenocortical carcinoma that was ectopically producing ACTH. This case emphasizes that physicians should have a broad-minded approach when evaluating cases of rare endocrine malignancies.
Numerical investigation on the deformation of railway embankment under normal faulting
Authors: Chen Haohua , Liu Jiankun , Li Zhijian , Liu Xiaoqiang , Nan Jiyun , Liu Jingyu
Published: July 2024

Active faults in the earthquake region are consistently regarded as a potential geological hazard to the construction and operation of railway engineering. However, the effects of normal faulting on railway embankments have not been investigated thoroughly. For bridging this knowledge gap, three-dimensional finite element analysis considering the influence of faulting offset, the soil layer’s thickness, the fault dip angle and the embankment cross-fault angle are conducted to clarify the normal faulting effects on the railway embankment. Emphasis is given to the stress and strain characteristic in the fault rupture outcropping regions on the embankment, the deformation of the embankment centerline for design purposes, and the determination of the affected zones for railway embankment preservation. The analysis shows that the normal fault rupture outcropping regions on railway embankment are tensile yield in most cases. The existence of the soil layer and its thickening would widen the affected zones and the regions where the fault ruptures outcrops. The fault dip angle and the cross-fault angle of the embankment have a complex effect on the behaviors of the crossing embankment. The depth of the subsidence zone of the embankment would increase with the decrease of the fault dip angle and the large fault dip angle would change the primary fault rupture to be a compressive one directly above the fault line. If the embankment crosses the fault line obliquely, the curvature radius of the centerline would hardly meet the design code.
Successful surgical treatment for aortoenteric fistula after esophagectomy: a case report
Authors: Nishimura Erica , Kawakubo Hirofumi , Ryota Asano , Masahi Takeuchi , Matsuda Satoru , Fukuda Kazumasa , Nakamura Rieko , Kitagawa Yuko
Published: July 2024

Background

An aortoenteric fistula (AEF) is a rare and lethal complication of esophagectomy. Fistulas frequently result from problems regarding acute infections or leaks, which are typically evident weeks after the treatment. However, some cases exhibit AEF years after the initial operation. Here, we describe a rare case of AEF caused by chronic friction of the stapler toward the aortic arch, in which stent graft repair and surgery were successful.

Case presentation

A 71-year-old man had undergone esophagectomy for esophageal carcinoma and reconstruction with a gastric conduit through the posterior mediastinal route 11 years previously. He visited our outpatient clinic with the chief complaint of hematemesis. However, after arrival, he experienced massive hematemesis and severe shock due to bleeding from an AEF. Endoscopic hemostasis using a Sengstaken-Blakemore tube followed by stent graft repair controlled the bleeding. We performed a partial resection of the gastric conduit, including the fistula, followed by digestive reconstruction using a jejunal interposition graft. The patient recovered gradually after receiving intensive care and was discharged 115 days after hospitalization.

Conclusions

We present a rare case of bleeding due to AEF long after esophagectomy, which was successfully treated with endovascular stent graft repair and surgery. Endoscopic hemostasis using a Sengstaken-Blakemore tube followed by stent graft repair was effective.
Financial Distress in Genitourinary Cancer: Insights From CDC National Health Interview Survey
Authors: Leonard Steven , Helstrom Emma , Correa Andres , Sindhani Mohit , Uzzo Nicole , Jia Angela Y. , Kutikov Alexander , Uzzo Robert , Psutka Sarah P. , Calaway Adam , Klaassen Zachary , Staehler Michael , Smaldone Marc , Wallis Christopher J.D. , Bukavina Laura
Published: July 2024

PURPOSE

This study leverages CDC National Health Interview Survey data to examine Financial Distress (FD) among genitourinary (GU) cancer survivors, specifically prostate cancer (PC), kidney cancer (KC), and bladder cancer (BC). It investigates the economic impacts faced by these patients, especially in relation to disparities in insurance coverage and its effects on material, psychological, and behavioral aspects of FD.

METHODS

We retrospectively analyzed responses from GU cancer survivors, stratifying by cancer status and age (18-64 years, ≥65 years). Medical financial hardship was divided into three domains: material, psychological, and behavioral. Associations between cancer history, hardship, and clinical factors were assessed using generalized ordinal logistic regressions.

RESULTS

Significant health care access disparities were found, particularly for mental health services, with 25% of younger BC survivors and 4.7% of younger KC survivors reporting affordability issues, in contrast to 2.7% of noncancer individuals. Dental care was also problematic, with higher avoidance rates among younger BC (27%) and KC (15%) survivors compared with the general population. Surprisingly, noncancer individuals reported more difficulty in affording prescriptions than BC survivors across both age groups. PC survivors, however, showed lower FD across all domains versus noncancer controls, indicating fewer concerns about medical bills and a lesser tendency to forgo care.

CONCLUSION

The study underscores significant gaps in the financial support system for GU cancer survivors, with urgent needs in mental and dental health care access. Policy interventions, including comprehensive insurance reforms, are imperative to alleviate the financial burdens on these individuals.
Two Centuries Have Shown That Voltaire May No Longer Be Correct About Doctors …At Least Those Treating Advanced Prostate Cancer
Authors: Trump Donald “Skip” , Raghavan Derek
Published: July 2024

Oncologists use molecular prediction/pharmacogenomics to improve Rx of cancer. Voltaire now wrong.
Mental Health Matters: Bringing Awareness to the Less Recognized Financial Toxicities of Cancer Care
Authors: Sears-Smith Megan , Knight Thomas G.
Published: July 2024

Discussing the less recognized financial toxicities of cancer care, including mental health and dental care
A Pediatric Case of Refractory Torsades de Pointes in Autoimmune Hypothyroidism
Authors: Chimatapu Sri Nikhita , Schachter Jessica L , Batra Anjan S , Sirignano Rachel , Okawa Erin R
Published: July 2024

Hypothyroidism can have a significant impact on cardiac contractility, vascular resistance, blood pressure, and cardiac rhythm. Ventricular arrhythmias induced by hypothyroidism are infrequently reported, especially in pediatric cases. A 15-year-old girl with autoimmune hypothyroidism experienced pulseless ventricular arrhythmias on 2 separate occasions because of nonadherence to levothyroxine medication. Subsequent investigations revealed an SCN5A mutation associated with Brugada syndrome. A loop recorder captured polymorphic ventricular tachycardia (PMVT), specifically Torsades de Pointes during her second event. Both arrhythmias were addressed only after stabilizing her thyroid hormone levels with replacement therapy. Although rare, patients with uncontrolled hypothyroidism may present with ventricular arrhythmias, particularly PMVT. The cornerstone of treatment for hypothyroidism-induced ventricular arrhythmia is thyroid replacement therapy. The identification of an SCN5A mutation unmasked by overt hypothyroidism emphasizes the need for a comprehensive cardiac evaluation in patients with hypothyroidism being assessed for PMVT.
Phrenic Nerve Block for Diaphragmatic Pain: Case Report
Authors: Thanaboriboon Chanon , Vargas Marta A. , Alexopoulos Konstantinos , Perez Jordi
Published: July 2024

Referred chronic shoulder pain may arise from diaphragmatic irritation. It can potentially be alleviated by blockade of the phrenic nerve. There is literature describing its use in acute pain conditions; yet for chronic pain, there are no reports. We present 2 cases of chronic diaphragmatic irritation causing ipsilateral referred shoulder pain. Patients experienced significant pain relief and a reduction in opioid consumption after receiving an ultrasound-guided phrenic nerve block. While the phrenic nerve block shows promise for pain relief, carefully evaluating its benefits and risks is recommended before considering its application in selected cases.
Cerebral Venous Sinus Thrombosis After Lumbar Epidural Steroid Injection: A Case Report
Authors: Xing Hanning , Babajanyan Henrik , Kuo Andrew , Bohnenblust Evan
Published: July 2024

Cerebral venous sinus thrombosis (CVST) is an exceedingly rare complication of epidural anesthesia, with only a handful of known cases after epidural steroid injection (ESI). We report a case of CVST in a 33-year-old male patient that presented with headache after lumbar ESI. His clinical status initially improved on anticoagulation in the intensive care unit. However, he had a sudden worsening of cerebral edema that required an emergent hemicraniectomy. Ultimately, the patient was pronounced dead by neurologic criteria. This case highlights the importance of keeping this rare but potentially fatal diagnosis in the differential even in lower-risk patient populations.
Historical Patterns in the Intergenerational Transmission of Lifespan and Longevity: A Research Note on U.S. Cohorts Born Between 1700 and 1900
Authors: Minardi Saverio , Corti Giulia , Barban Nicola
Published: July 2024

This research note examines historical trends in lifespan inequality and the intergenerational transmission of lifespan and longevity in the United States over the eighteenth, nineteenth, and twentieth centuries. We contribute to the literature by expanding the estimates of the familial component beyond parent–child associations to include multigenerational and horizontal classes of relatives of different sexes. We also examine how lifespan inequality and the role of the family in lifespan and longevity changed over time. We address the challenge of studying extended family networks in historical times by leveraging recent online crowdsourced genealogical data. Results confirm the presence of a familial component for all classes of relatives considered and highlight a stronger association for horizontal than for vertical relationships. Despite decreasing lifespan inequality, we find no evidence of decreased familial lifespan stratification throughout history. If anything, the results suggest a strengthening of the parent–child association. Finally, the results contribute to the debate on the representativeness and usability of crowdsourced genealogical data by emphasizing the importance of sample selection based on the quality of the information collected.
Predictive Value of Bolster Supine X-Ray for the Correction of Segmental Deformity After Thoracolumbar Fusion Surgery
Authors: Lee Sang Hyub , Kim Dong-Hwan , Park Jin Hoon , Kang Dong Ho
Published: July 2024

BACKGROUND AND OBJECTIVES:

Assessment of thoracolumbar spine flexibility is crucial for determining which osteotomy to perform (posterior column osteotomy or 3-column osteotomy) to restore sagittal balance. Although preoperative bolster supine X-rays have been used to evaluate spine flexibility, their correlation with postoperative spinopelvic parameters has not been reported. We aimed to evaluate the predictive value of bolster X-ray for correcting sagittal deformities after thoracolumbar fusion surgery.

METHODS:

We retrospectively evaluated patients who underwent bolster supine radiography before posterior thoracolumbar fusion. Demographic data, operative records, and radiographic parameters were also recorded. The segmental Cobb angle, defined as the angle between the upper endplate of the uppermost and lower endplates of the lowest instrumented vertebrae, was compared between bolster and postoperative X-ray to evaluate the correlation between them. The predictive value of bolster X-ray for postoperative deformity correction was measured using intraclass correlation coefficients (ICC).

RESULTS:

Forty-two patients were included. The preoperative segmental Cobb angle (−1.4 ± 22.4) was significantly lower than the bolster segmental Cobb angle (23.2 ± 18.7, P < .001) and postoperative segmental Cobb angle (27.9 ± 22.3, P < .001); however, no significant difference was observed between the bolster and postoperative segmental Cobb angles (P = .746). Bolster X-ray showed a very strong correlation with postoperative X-ray (r = 0.950, P < .001) for segmental Cobb angle. Bolster supine X-ray had good-to-excellent reliability for postoperative X-ray with an ICC of 0.913 (95% CI, 0.760-0.962, P < .001) for the segmental Cobb angle.

CONCLUSION:

Bolster supine X-rays demonstrate good-to-excellent reliability with postoperative X-rays for segmental Cobb angles. These findings offer valuable insights into the selection of appropriate osteotomy techniques for clinical practice.
An International, Multicenter Feasibility Study on Active and Continuous Irrigation With Cerebrospinal Fluid Exchange for Improving Outcomes in Cerebral Ventriculitis
Authors: Baig Ammad A. , Hess Ryan M. , Sprau Annelise C. , Kemeny Hanna , Hashmi Eisa , Nazari Pouya , Lim Jaims , Turner Ryan C. , Brandmeir Nicholas , Rezai Jahromi Behnam , Niemelä Mika , Jahromi Babak S. , Levy Elad I. , Siddiqui Adnan H.
Published: July 2024

BACKGROUND AND OBJECTIVES:

Cerebral ventriculitis remains a challenging neurosurgical condition because of poor outcomes including mortality rates of nearly 80% and a prolonged course of treatment in survivors. Despite current conventional management, outcomes in some cases remain unsatisfactory, with no definitive therapeutic guidelines. This feasibility study aims to explore the use of a novel active, continuous irrigation and drainage system (IRRAflow [IRRAS AB]) combined with intraventricular drug delivery for patients with cerebral ventriculitis.

METHODS:

We conducted a multicenter, international, retrospective study of patients with ventriculitis who were treated with use of the IRRAflow system. Data collected included patient demographics, comorbidities, admission Glasgow Coma Scale score, baseline modified Rankin Scale (mRS) score, and imaging findings. Catheter occlusions, infections, and shunt placement were recorded for outcome assessment, along with discharge mRS scores and in-hospital deaths.

RESULTS:

Four centers contributed data for a total of 21 patients who had IRRAflow placement for treatment of ventriculitis. Thirteen (61.9%) were men (mean age = 49.8 ± 14.87 years). The median baseline mRS score was 1. The median Glasgow Coma Scale score at admission was 13. The etiology of ventriculitis was iatrogenic in 12 (57.1%) patients and secondary to an abscess in 9 (42.9%). No cases reported hemorrhage or failure of IRRAflow placement. Antibiotics were administered through the IRRAflow system in 13 (61.9%) cases in addition to systemic dosing. Sixteen (76.2%) patients had significant clinical improvement and resolution of ventriculitis. Seven (33.3%) patients required shunt placement after resolution because of persistent hydrocephalus. There were 6 (28.6%) in-hospital deaths.

CONCLUSION:

The use of active irrigation with drainage for continuous delivery of intraventricular irrigation fluid with antibiotics led to dramatically low mortality. In our case series, it led to a marked improvement in neurological status, imaging findings, and cerebrospinal fluid profiles, making it a technically feasible and safe treatment for ventriculitis.
Evolution of the regulation of developmental gene expression in blind Mexican cavefish
Authors: Leclercq Julien , Torres-Paz Jorge , Policarpo Maxime , Agnès François , Rétaux Sylvie
Published: July 2024

Developmental evolution and diversification of morphology can arise through changes in the regulation of gene expression or protein-coding sequence. To unravel mechanisms underlying early developmental evolution in cavefish of the species Astyanax mexicanus, we compared transcriptomes of surface-dwelling and blind cave-adapted morphs at the end of gastrulation. Twenty percent of the transcriptome was differentially expressed. Allelic expression ratios in cave X surface hybrids showed that cis-regulatory changes are the quasi-exclusive contributors to inter-morph variations in gene expression. Among a list of 108 genes with change at the cis-regulatory level, we explored the control of expression of rx3, which is a master eye gene. We discovered that cellular rx3 levels are cis-regulated in a cell-autonomous manner, whereas rx3 domain size depends on non-autonomous Wnt and Bmp signalling. These results highlight how uncoupled mechanisms and regulatory modules control developmental gene expression and shape morphological changes. Finally, a transcriptome-wide search for fixed coding mutations and differential exon use suggested that variations in coding sequence have a minor contribution. Thus, during early embryogenesis, changes in gene expression regulation are the main drivers of cavefish developmental evolution.
A large-scale CRISPR screen reveals context-specific genetic regulation of retinal ganglion cell regeneration
Authors: Emmerich Kevin , Hageter John , Hoang Thanh , Lyu Pin , Sharrock Abigail V. , Ceisel Anneliese , Thierer James , Chunawala Zeeshaan , Nimmagadda Saumya , Palazzo Isabella , Matthews Frazer , Zhang Liyun , White David T. , Rodriguez Catalina , Graziano Gianna , Marcos Patrick , May Adam , Mulligan Tim , Reibman Barak , Saxena Meera T. , Ackerley David F. , Qian Jiang , Blackshaw Seth , Horstick Eric , Mumm Jeff S.
Published: July 2024

Many genes are known to regulate retinal regeneration after widespread tissue damage. Conversely, genes controlling regeneration after limited cell loss, as per degenerative diseases, are undefined. As stem/progenitor cell responses scale to injury levels, understanding how the extent and specificity of cell loss impact regenerative processes is important. Here, transgenic zebrafish enabling selective retinal ganglion cell (RGC) ablation were used to identify genes that regulate RGC regeneration. A single cell multiomics-informed screen of 100 genes identified seven knockouts that inhibited and 11 that promoted RGC regeneration. Surprisingly, 35 out of 36 genes known and/or implicated as being required for regeneration after widespread retinal damage were not required for RGC regeneration. The loss of seven even enhanced regeneration kinetics, including the proneural factors neurog1, olig2 and ascl1a. Mechanistic analyses revealed that ascl1a disruption increased the propensity of progenitor cells to produce RGCs, i.e. increased ‘fate bias’. These data demonstrate plasticity in the mechanism through which Müller glia convert to a stem-like state and context specificity in how genes function during regeneration. Increased understanding of how the regeneration of disease-relevant cell types is specifically controlled will support the development of disease-tailored regenerative therapeutics.
Testing in Intermittent Sports—Importance for Training and Performance Optimization in Adult Athletes
Authors: VIGH-LARSEN JEPPE F. , JUNGE NICKLAS , CIALDELLA-KAM LYNN , TOMÁS RITA , YOUNG LAURA , KRUSTRUP PETER , MOHR MAGNI , NYBO LARS
Published: July 2024

Performance in intermittent sports relies on the interplay between multiple physiological systems determining the capacity to perform short explosive efforts as well as repeated intense actions with limited recovery over the course of an entire game. Testing should reflect these demands to allow for sport- and position-specific capacity analyses that eventually may translate into optimized training and improved performance. This may include individual load management and optimized training prescription, intensity targeting for specific positions or individual athletes, as well as benchmarking for monitoring of training progression and enhanced engagement of athletes. This review provides an overview of available tests in different exercise domains identified as relevant (from assessment of single explosive actions to intermittent endurance capacity), forming the basis for recommendations on how to compose a comprehensive yet feasible test battery that may be integrated into the seasonal competition and training plan. The test procedures should cover the performance spectrum of relevance for the individual athlete—also in team sports to account for positional differences. We emphasize the benefits of sport-specific tests, highlight parameters of importance for test standardization, and discuss how the applied test battery may be supplemented with secondary tests directed toward specific energy systems to allow for more in-depth analyses when required (e.g., in terms of an underperforming athlete). The synergy between testing and tracking of match performance (utilizing time-motion or global positioning systems) is highlighted, and although tracking cannot substitute for testing, combining the tools may provide a comprehensive overview of the physiological demands and performance during competition contextualized to the athletes’ maximal exercise capacity.
Μελέτη του ρόλου της ομάδας των Minibrain/DYRK κινασών στην ανάπτυξη του νευρικού συστήματος
Authors: Κοκκοράκης Νικόλαος
Published: July 2024

Η διασταυρούμενη επίδραση μεταξύ της κινάσης Mirk/Dyrk1B και του σηματοδοτικού μονοπατιού Sonic hedgehog (Shh)/Gli επηρεάζει τη φυσιολογία και την παθολογία. Τα ευρήματα της παρούσας διδακτορικής διατριβής αποκαλύπτουν ένα νέο ρόλο για την κινάση Dyrk1B στη ρύθμιση των κοιλιακών προγονικών και νευρωνικών υποτύπων στον εμβρυϊκό νωτιαίο μυελό του κοτόπουλου διαμέσου του μονοπατιού Shh. Αρχικά, διερευνήθηκε το αναπτυξιακό πρότυπο έκφρασης της κινάσης Dyrk1B στο ΚΝΣ του ποντικού και του κοτόπουλου κατά τη διάρκεια της εμβρυογένεσης, μεταγεννητικής και ενήλικης ζωής. Δείχθηκε ότι η κινάση Dyrk1B εκφράζεται από τους πολλαπλασιαζόμενους νευροβλάστες και τους μεταμιτωτικούς νευρώνες του εγκεφάλου και του νωτιαίου μυελού και ότι η έκφρασή της στην οδοντωτή έλικα του εγκεφάλου του ποντικού σηματοδοτεί όλα τα στάδια της δευτερογενούς και ενήλικης νευρογένεσης. Επιπροσθέτως, η έκφραση της Dyrk1B μειώνεται κατά τη διάρκεια της ανάπτυξης του ΚΝΣ του ποντικού και του κοτόπουλου υποδεικνύοντας ένα σημαντικό ρόλο της κινάσης Dyrk1B στα πρώτα στάδια της νευρογένεσης. Προσεγγίσεις in ovo ‘προσθήκης’ και ‘απώλειας λειτουργίας’ (gain-and-loss-of-function approaches) στο αναπτυξιακό στάδιο E2 έδειξαν ότι η κινάση Dyrk1B επηρεάζει τον πολλαπλασιασμό και τη διαφοροποίηση των νευρωνικών προγονικών κυττάρων στο στάδιο E4 και επιδρούν στην απόπτωση, ειδικά στην περιοχή των κινητικών νευρώνων (motor neuron domain). Ειδικότερα, η υπερέκφραση της κινάσης Dyrk1B ελαττώνει τους αριθμούς των κοιλιακών προγονικών κυττάρων, των κινητικών νευρώνων και των ενδιάμεσων νευρώνων V2a, ενώ η φαρμακολογική αναστολή της ενεργότητας κινάσης της ενδογενούς Dyrk1B από τη χορήγησης του ειδικού αναστολέα της, AZ191, αυξάνει τους αριθμούς των κοιλιακών προγονικών κυττάρων και των κινητικών νευρώνων. Μηχανιστικά, η υπερέκφραση της κινάσης Dyrk1B καταστέλλει τα επίπεδα mRNA του μορφογόνου Shh και των τελεστών Gli2 και Gli3, ενώ αντιθέτως, η μεταγραφή των Shh, Gli2 και Gli3 αυξάνεται παρουσία του αναστολέα της κινάσης Dyrk1B AZ191 ή του αγωνιστή της πρωτεΐνης Smoothened, SAG. Πιο σημαντικά, στα πειράματα ‘διάσωσης φαινοτύπου’ (phenotype rescue experiments), ο αγωνιστής SAG αποκαθιστά τη διαμεσολαβούμενη από την κινάση Dyrk1B απορρύθμιση των κοιλιακών προγονικών κυττάρων. Επίσης, στο στάδιο E6, η κινάση Dyrk1B επηρεάζει εκλεκτικά το μέγεθος της μεσαίας πλευρικής κινητικής στήλης (medial lateral motor column, LMCm), στην οποία και αποδείχθηκε η περιορισμένη έκφραση του μορφογόνου Shh στην ηλικία αυτή. Συμπερασματικά, αυτές οι παρατηρήσεις αποκαλύπτουν μία νέα ρυθμιστική λειτουργία της κινάσης Dyrk1B στην καταστολή του σηματοδοτικού μονοπατιού Shh/Gli επηρεάζοντας, συνεπώς, τα κοιλιακά προγονικά κύτταρα του αναπτυσσόμενου νωτιαίου μυελού. Αυτά τα δεδομένα καθιστούν την κινάση Dyrk1B έναν πιθανό θεραπευτικό στόχο για τις ασθένειες των κινητικών νευρώνων.
Comparative evaluation and correlation of variations in articular disc morphology as assessed by automated segmentation using deep learning on magnetic resonance imaging (MRI) images in Class II (vertical) TMD cases, Class II (horizontal) TMD cases and Class I non-TMD cases
Authors: Surendran Aathira , Shrivastav Sunita , Srivastav Gaurav
Published: July 2024

Introduction: Temporomandibular disorder (TMD) encompasses several clinical manifestations, which are characterized by temporomandibular joint and masticatory muscle discomfort and dysfunction (TMJ). The best imaging technique for evaluating TMJ is magnetic resonance imaging (MRI), which makes it possible to see the anatomical and pathological characteristics of every joint component. In recent years, convolutional neural networks -based deep learning algorithms have been favoured because of their outstanding capability in recognizing objects in medical images. The objective of this study is to assess, compare and co-rrelate articular disc morphology by automated segmentation using deep learning on MRI images in skeletal Class II (vertical growth pattern) TMD cases as compared to skeletal Class II (horizontal growth pattern) TMD cases and Class I non-TMD cases Methods: Grading of skeletal Class II (vertical growth pattern) cases and skeletal Class II (horizontal growth pattern) cases based on severity of TMD will be carried out using diagnostic criteria for temporomandibular disorders. Bilateral sagittal as well as coronal MRI images will be obtained. A convolutional neural network (CNN) encoder-decoder named U-Net will be used to segment the articular disc on MRI. Understanding the nature of variations between Class I and both types of Class IIs will help orthodontists to better predict the potential risk for the development of TMDs and accordingly take precautions while doing treatment in such cases. Moreover, it can be used to automate TMD diagnosis and other smart applications. Conclusions: This study will aid in identifying articular disc morphology on MRI. The deep learning algorithms with effective data augmentation may perform better in MRI readings than human clinicians when using the same data, which will be advantageous for TMD diagnosis.
A study on health care utilization out-of-pocket expenditure in rural central India: A cross-sectional study
Authors: Hepat Ankita , Chakole Dr. Swarupa
Published: July 2024

Background Out-of-pocket health expenditures have significant adverse effects, potentially resulting in impoverishment and impacting the quality of life. Awareness of patterns of healthcare utilization and out-of-pocket expenses is essential for informing healthcare scheme decisions. According to estimates from the World Health Organization in 2005, illness and the financial strain of healthcare costs force 25 million households into poverty each year. The goal of the study is to assess the proportion of households incurring out-of-pocket expenditure (OOPE) and The mean quality expended by households on healthcare. Methods In Wardha district, a cross-sectional study will be conducted. The pre-tested semi-structured survey will be administered to examine a sample of adult age groups, to identify sociodemographic data, utilization of healthcare services, and OOPE. A sample of 246 participants was selected by random sample method. Conclusion This study will help to improve and assess healthcare utilization and reduce out-of-pocket expenditures that lead to catastrophe and impoverishment. Awareness of the participants about health insurance. And they were known about the healthcare services.
Enabling equitable and affordable access to novel therapeutics for pandemic preparedness and response via creative intellectual property agreements
Authors: Griffen Ed J. , Boulet Pascale ,   ASAP Discovery Center,   COVID Moonshot
Published: July 2024

The COVID-19 pandemic demonstrated that the current purely market-driven approaches to drug discovery and development alone are insufficient to drive equitable access to new therapies either in preparation for, or in response to, pandemics. A new global framework driven by equity is under negotiation at the World Health Organization to support pandemic preparedness and response. Some believe that the global intellectual property (IP) system itself is part of the problem and propose a purely Open Science approach. In this article, we discuss how existing IP frameworks and contractual agreements may be used to create rights and obligations to generate a more effective global response in future, drawing on experience gained in the COVID Moonshot program, a purely Open Science collaboration, and the ASAP AViDD drug discovery consortium, which uses a hybrid, phased model of Open Science, patent filing and contractual agreements. We conclude that ‘straight to generic’ drug discovery is appropriate in some domains, and that targeted patent protection, coupled with open licensing, can offer a route to generating affordable and equitable access for therapy areas where market forces have failed. The Extended Data contains a copy of our model IP policy, which can be used as a template by other discovery efforts seeking to ensure their drug candidates can be developed for globally equitable and affordable access.