bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Stopping Medications and Introducing a Whole Food Plant-Based Diet on Patients Living with Multiple Sclerosis – A Report of Two Cases
Authors: Cuthbert Monty , Lewandowska Marta , Freeman Laura , Devine Conor , Lee Karen , Kassam Shireen
Published: December 2022

More than 2 million people live with multiple sclerosis worldwide and the prevalence has been increasing over time. Patients living with multiple sclerosis often explore diet and lifestyle interventions as a means of managing their symptoms and reducing reliance on medication; yet, these approaches are rarely discussed with their physicians. Currently, there is a lack of evidence on when to stop disease-modifying therapies (DMT), and recent research showed no statistically significant difference in the time between relapses when comparing participants who stopped DMT to those who did not, especially over the age of 45. This case report presents 2 patients with multiple sclerosis who made an informed decision to stop their DMT medications and have been managing their condition with a whole food plant-based diet and a healthy lifestyle approach. Over the period of 5 to 6 years since stopping the medications, each patient only had 1 multiple sclerosis flare-up to date. In the report, the focus is on the impact of diet on multiple sclerosis. It adds to currently available literature and encourages further research in the field of managing multiple sclerosis with lifestyle interventions.
Construction of a prognostic classifier and prediction of the immune landscape and immunosuppressive molecules in gliomas based on combination of inflammatory response-related genes and angiogenesis-associated genes
Authors: Chen Chunbao , Du Xue , Liu Hongjun , Lu Xingyu , Li Dong , Qi Jian
Published: December 2022

Objective:We aimed to combine inflammatory response-related genes (IRRGs) and angiogenesis-associated genes (AAGs) to build a prognostic classifier and to predict immune landscapes and immunosuppressive molecules in gliomas.

Introduction: Gliomas, the commonest primary brain tumors, account for about 80% of cancerous tumors in the central nervous system (CNS), featuring rapid progression, high malignancy, and extremely poor prognosis. The induction of inflammatory responses and angiogenesis have been considered to be closely related to tumors. However, there are little publications systematically elaborating on their impacts on gliomas.

Methods: We downloaded the data of IRRGs and AAGs from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases, and retrieved 68 differentially expressed genes (DEGs), of which 13 DEGs pertained to the prognosis of glioma cases. Next, 9 DEGs were screened from the 13 major DEGs with predictive significance and utilized to build a 9-gene signature as a prognostic risk score model (PRSM) with the aid of univariate Cox regression analyses (CRA) and least absolute shrinkage and selection operator (LASSO)-CRA. On this basis, glioma patients fell into high-risk (HR) group and low-risk (LR) group. Later, we implemented Gene Set Enrichment Analysis (GSEA, Gene Set: WP_ANGIOGENESIS) and calculate the scores of cell infiltration and immune-associated function by harnessing single-sample GSEA (ssGSEA).

Results: The prognosis was compared between the two groups by introducing Kaplan-Meier (KM) analysis, which yielded that HR group exhibited poorer prognosis. Additionally, the predictive capacity and independent characteristics were proven by the receiver operating characteristic curve (ROC) and multivariate CRA. Further, We took an evaluation of immune profiles, which unraveled that immunosuppressive cell count was distinctively larger in HS group. Finally, a protein-protein interaction (PPI) network of DEGs was built, and 10 hub genes were obtained, of which epidermal growth factor receptor (EGFR) was closely related to poor prognosis.

Conclusion: A 9-gene signature was established on the strength of IRRGs and AAGs for predicting glioma prognosis, tumor microenvironment (TME), immune landscapes and immunosuppressive molecules. However, the molecular mechanism developed by this signature to function in tumor immunity needs further experimental research in the future and is expected to be a research target for glioma immunotherapy strategies.
Anaesthetics and time perception: A review
Authors: Wehrman Jordan J , Chung Clara C , Sanders Robert
Published: December 2022

Consciousness requires subjective experience in the “now.” Establishing “now,” however, necessitates temporal processing. In the current article, we review one method of altering consciousness, anaesthetic drug administration, and its effects on perceived duration. We searched PubMed, PsycInfo, and ScienceDirect databases, and article reference sections, for combinations of anaesthetic drugs and time perception tasks, finding a total of 36 articles which met our inclusion criteria. We categorised these articles with regard to whether they altered the felt passage of time, short or long interval timing, or were motor timing tasks. We found that various drugs alter the perceived passage of time; ketamine makes time subjectively slow down while GABAergic drugs make time subjectively speed up. At a short interval there is little established evidence of a shift in time perception, though temporal estimates appear more variable. Similarly, when asked to use time to optimise responses (i.e., in motor timing tasks), various anaesthetic agents make timing more variable. Longer durations are estimated as lasting longer than their objective duration, though there is some variation across articles in this regard. We conclude by proposing further experiments to examine time perception under altered states of consciousness and ask whether it is possible to perceive the passage of time of events which do not necessarily reach the level of conscious perception. The variety of methods used raises the need for more systematic investigations of time perception under anaesthesia. We encourage future investigations into the overlap of consciousness and time perception to advance both fields.
Notes towards a historical, critical theory of memory constellations: Postcolonial nationalist memory in Michael Anthony’s King of the Masquerade
Authors: Wegner Jarula MI
Published: December 2022

The historical and critical theory of memory constellations addresses two challenges in cultural memory studies: the detachment of memories from socio-historical contexts and the risk of critical concepts becoming dogmatic. Instead of imposing a memory concept top-down, memory constellations analyse cultural memories from the bottom-up by triangulating these with their historical precedents and the social conditions that enable the memories to emerge. The tensions, conflicts and contradictions between memory, genealogy and social conditions enable a fundamentally historical critique. The description of the steelpan in Michael Anthony’s novella King of the Masquerade and wider societal as well as transnational dynamics reveals a memory war that can be described as a memory constellation of postcolonial nationalist remembrance.
‘Sharing for the memories’: Contemporary conceptualizations of memories by young women
Authors: Annabell Taylor
Published: December 2022

This article examines how young women conceptualize memories within their language use. Through a microanalysis of how the term ‘memories’ and related expressions are mobilized by participants in interviews and digital traces shared on platforms, the study offers insight into everyday articulations of memory. The term ‘memories’ not only denotes the selective reconstruction of the past in the present but also signals how certain experiences, moments and feelings are assessed as worth remembering. Talking about ‘memories’ becomes a way for young women to signify and anticipate the value of experience in the present and future. In making this argument, the article contributes to existing debates on metaphors of memory and the production of memories through mediated objects by demonstrating how mnemonic language is reconfigured within digital culture.
Memory laws, mnemonic weapons: The diffusion of a norm across Europe and beyond
Authors: Lucksted Danielle
Published: December 2022

The diffusion of memory laws across Europe maps onto global trends towards legal memory protection writ large. Through applications of cosmopolitan memory and norm diffusion, this article demonstrates that differences across laws – although they derive language and sentiment from a shared global norm – also adhere to the specific memory politics of the state. The author proposes that three categories of memory law have emerged since the 1980s, each resulting from isomorphic pressures exerted by an international community with expectations of shared sociolegal human rights norms. The article concludes with a case study of recent laws in Russia (2014) and Poland (2018): both illustrative of a new nationalistic paradigm of memory laws as mnemonic weapons in ongoing memory wars. By tracing isomorphic similarities across Europe, this article reveals a mirroring of language that has recently appeared in the United States. It is with an eye towards worldwide shifts in populism that the current research remains urgent. This study offers a theoretical contribution from which memory scholars might draw when considering globally relevant mnemonic trends.
Mnemonic wars and parallel polis: The anti-politics of memory in Central and Southeast Europe: Kosovar women and Black/Roma Lives Matter
Authors: Kola Adam F , Domachowska Agata , Gemziak Łukasz , Trupia Francesco
Published: December 2022

The essay argues that anti-politics, a category borrowed from the anti-communist movement in the Eastern Bloc, can inspire memory studies. We focus on one of the chosen categories – the parallel polis (with some forays into the matter of the nonviolence movement). We discuss this universal category through the particular lens of Central and Southeast Europe with two examples: (1) women’s memories of war and violence in Kosovo with a specific focus on the Heroinat monument in Pristina and (2) the Black Lives Matter movement in Czechia that can be used to highlight the racially and ethnically motivated activities of the police, as well as oblivion of the Holocaust of the Roma community in mainstream discourse. It all leads to the identification of parallel orders of memory produced by marginalized groups, as well as the development of anti-politics of memory in opposition to the official, state-driven politics of memory.
Resorbable magnesium screws for fixation of medial epicondyle avulsion fractures in skeletally immature patients: A comparison with Kirschner wires
Authors: Baldini Marco , Coppa Valentino , Falcioni Danya , Cusano Giuseppe , Massetti Daniele , Marinelli Mario , Gigante Antonio Pompilio
Published: December 2022

Background:

Displaced medial epicondyle fractures are treated with open reduction and internal fixation with K-wires or screws. Rates of implant prominence, failure, or non-union reported are considerable. Magnesium screws have demonstrated biocompatibility, osteoconductivity, and high pull-out strength. The aim of this study was to compare surgical fixation of medial epicondyle fracture using resorbable magnesium Herbert screws to K-wires, in skeletally immature patients.

Methods:

A retrospective analysis was performed from January 2015 to April 2020. Inclusion criteria were as follows displaced medial epicondyle fracture, <15 years, and absence of concomitant ipsilateral upper limb fractures. Two consecutive cohorts based on fixation device were made: Group A (wires) and Group B (magnesium screws). Alignment, pain, range of motion, Mayo Elbow Performance Score, and radiological healing were assessed.

Results:

A total of 27 patients were included: 15 in Group A and 12 in Group B. Groups were comparable for age and sex. Mean follow-up was higher in Group A (38.73 ± 3.15 vs 26.18 ± 4.85 months; p < 0.001). No significant differences were observed regarding range of motion, alignment, pain, and Mayo Elbow Performance Score, with excellent results in both groups. Two patients in Group A developed a deep wound pin site infection requiring antibiotics. X-rays revealed three cases of non-union in Group A and one in Group B, all of them asymptomatic. No patient required a second surgical procedure.

Conclusion:

Open reduction and internal fixation of medial epicondyle fractures with magnesium screws showed comparable results to a widely accepted procedure such as the use of K-wires, potentially with a lower incidence of non-union and infection. No adverse reactions were recorded.

Level of evidence:

level III.
Curcumin-Nicotinate Attenuates Hippocampal Synaptogenesis Dysfunction in Hyperlipidemia Rats by the BDNF/TrkB/CREB Pathway: Involving Idol/LDLR Signaling to Eliminate Aβ Deposition
Authors: Wang Lin-Yu , Liu Jiao , Peng Yi-Zhu , Zhang Cai-Ping , Zou Wei , Liu Feng , Zhan Ke-Bin , Zhang Ping
Published: December 2022

Hyperlipidemia has been demonstrated to evoke Alzheimer disease (AD) pathologies such as Amyloid-β (Aβ) deposition and synaptogenesis dysfunction in the hippocampus. Curcumin gives protection against anti-amyloid properties and synaptogenesis dysfunction. Curcumin-Nicotinate (CurTn), a new type of curcumin derivative, ameliorates cognitive impairment by rescuing autophagic flux in the CA1 hippocampus of diabetic rats. However, whether Curtn possesses an antagonistic effect on AD-related pathologies in the hippocampus induced by hyperlipidemia remains ill-defined. The present study aims to investigate whether CurTn alleviates synaptogenesis dysfunction by promoting the activation of brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB)/cAMP-response element binding protein (CREB) signaling and whether the underlying fundamental mechanism involves the elimination of Aβ deposition due to Idol/low-density lipoprotein receptor (LDLR) signaling in the hippocampus of high-fat diet (HFD)-induced hyperlipidemia rats. The results demonstrated that CurTn not only improved synaptogenesis dysfunction in the hippocampus of HFD rats, as evidenced by the increases in the expressions of synapse-related proteins postsynaptic density protein 95 (PSD-95), synapsin-1, and Glutamate receptor 1 (GluR1), but also activated BDNF/TrkB/CREB signaling, as evidenced by the elevation of the expressions of BDNF, pTrkB, and CREB. Moreover, CurTn modulated the Idol/LDLR pathway in the hippocampus of HFD rats, as evidenced by the decreased expression of Idol and the increased expression of LDLR. Furthermore, CurTn eliminated the deposition of Aβ, as evidenced by the reduction in the content of Aβ40 and Aβ42. These results reveal that CurTn may attenuate synaptogenesis dysfunction by activating BDNF/TrkB/CREB signaling, as the possible result of the modulation of Idol/LDLR signaling to eliminate Aβ deposition in the hippocampus of HFD rats.
Ethnopharmacology, Phytochemistry, and Pharmacological Activities of Spatholobus suberectus Vine Stem
Authors: Nguyen-Ngoc Hieu , Vu-Van Tuan , Pham-Ha-Thanh Tung , Le-Dang Quang , Nguyen-Huu Tung
Published: December 2022

Spatholobus suberectus vine stem is an important medicinal material in Chinese, Vietnamese, and Korean traditional medicines. Its decoction has long been used to treat blood disorders, such as anemia and menstrual irregularity, as well as rheumatoid diseases. Previous phytochemical investigations characterized 88 compounds from S suberectus, which mainly belonged to the phenolic class, especially of the flavonoid type. Pharmacological studies showed the beneficial effects of extracts of the plant on the cardiovascular tract, which is ethnopharmacologically relevant to the plant's use in traditional medicine. Besides that, the extracts and isolated compounds also exhibited antimicrobial, anticancer, antiinflammatory, and antioxidant activities. The past study results support the use of S suberectus vine stem in traditional medicine and also revealed new directions of pharmacological effects of this medicinal plant.
The urban sediments of Karlsplatz, Vienna (Austria) as a reference section for the Anthropocene series
Authors: Wagreich Michael , Meszar Maria , Lappé Kira , Wolf Janis , Mosser Martin , Hornek Katrin , Koukal Veronika , Litschauer Constance , Piperakis Nikolaos , Hain Karin
Published: December 2022

Anthropogenic strata form the layered urban archive in the underground of large cities. In a transdisciplinary project involving geosciences, isotope physics and urban archaeology, we looked for artificial isotopes and anthropogenic trace metals. The tested archaeological site Karlsplatz is situated in the city of Vienna (Austria). Archaeology and historical data sets provide age constraints around 1922, post-1945 and at 1959. A layer on top of the WW2 rubble that covers foundations of a 1922 building post-dates 1945, and pre-dates the levelling of the artificial park ground in 1959. The fine-grained sediment matrix of these layers is mixed with backfilled soil material. Samples were analysed for trace elements such as lead, copper and zinc, and prepared for chemical separation of actinides analysed by Accelerator Mass Spectrometry (AMS). Several artificial radionuclides, including the plutonium and uranium isotopes 239Pu, 240Pu and 236U, were found in the post-1945 layer, and the 240Pu/239Pu isotope ratio clearly points to the presence of atmospheric atomic bomb fallout material of the 1950s. Thus, the bomb-spike can be identified and used as a primary stratigraphic marker even in coarse urban anthropogenic sediments, exemplifying the correlation potential of these radionuclide markers and marking a correlative reference section for the Anthropocene series.
Smartphone application-based follow-up care of patients after bariatric surgery: A mixed-method study of usability
Authors: Yang Cui , Kessler Mia , Taebi Niki , Moorthy Preetha , Reissfelder Christoph , Otto Mirko , Vassilev Georgi
Published: December 2022

Objective

Due to potential short-term and long-term complications, adequate lifelong follow-up is crucial for patients after bariatric surgery. However, compliance with postoperative follow-up is poor despite clear national and international guidelines. This feasibility trial aimed to evaluate the usability of a smartphone application-based follow-up program in patients after bariatric surgery.

Methods

Patients were included after having undergone a primary bariatric surgery. Instead of attending meetings in our outpatient clinic, they were followed up using a smartphone application. After 6 months, the System Usability Scale (SUS) was used to measure participant perception. Additional interviews were performed to gain more insight into the usability of the app.

Results

Between August 2020 and February 2021, 52 patients met the inclusion criteria and agreed to participate in the study, of whom 5 (9.6%) dropped out of the study. At the time of analysis, 31 patients have been followed up for 6 months, among whom 26 patients completed the SUS questionnaire. The mean overall score of SUS is 82.1 ± 19.8. In the qualitative analysis, participants were generally positive about the follow-up care and found it easy to use, despite some minor technical problems.

Conclusion

Our smartphone app-based follow-up program was proven to be effective in the aftercare succeeding bariatric surgery. Our data indicates that the satisfaction, efficiency, learnability, and ease of use of the smartphone application were coherent in the acceptance and use of mobile technology by patients.
Factors associated with the adoption of a digital health service by patent proprietary medicine vendors (PPMVs) in Lagos, Nigeria
Authors: Agha Sohail , Ruiz-Gaona Laura Alejandra , Friedman Jed , Cheikh Nejma , Gorgens Marelize
Published: December 2022

Background

Patent proprietary medicine vendors (PPMVs) are the first point of care for low-income Nigerian households. They are likely to have an important role in a digital care pathway established for low-income Nigerian women and children. Yet, little is known about what drives the adoption of digital platforms by PPMVs.

Methods

This study explores factors associated with the adoption of a digital service, NaijaCare, created to enable PPMVs to increase the range and quality of products and services they offer. A structured, quantitative, face-to-face survey was conducted among 248 PPMVs in Lagos in February and March 2020. Multivariate analysis was conducted to identify factors associated with the adoption of NaijaCare.

Results

Women comprise the majority (67%) of medicine vendors in Lagos. Most medicine vendors (64%) had gotten health training on the job. About a quarter (27%) of medicine vendors reported seeking business advice on the internet. Medicine vendors who had obtained on-the-job training had a 12.31 times higher odds ratio ( p < 0.01) of adopting the digital service. Medicine vendors who sought business advice on the internet had a 6.48 times higher odds ratio ( p < 0.001) of adopting NaijaCare.

Conclusion

The study findings suggest that PPMVs’ use of the digital service was driven by their desire to increase business profits. Digital care pathways targeting low-income households should be aligned with the business interests of informal providers.
Democratic backsliding in the Philippines: Are voters becoming illiberal?
Authors: Kasuya Yuko , Calimbahin Cleo Anne A
Published: December 2022

Democratic backsliding by incumbents is one of the most prevalent forms of backsliding in recent global trends of democratic erosion. Understanding the attitude of voters toward backsliding incumbents is crucial because popular support is the basis of legitimacy for these incumbents. This article studies voter attitudes in the Philippines, where democracy was subverted by the incumbent president, Rodrigo Duterte, who served from 2016 to 2022. Specifically, we examine the validity of the claim that Filipino voters are acquiring a “taste for illiberal rule” made by some scholars. First, we analyzed the survey data regarding the support for various types of political systems, where part of the data comes from our originally commissioned survey at the Social Weather Stations. Second, we explored Pulse Asia's longitudinal survey data on martial-rule support. Our investigation of these survey data did not find substantive support for the “taste for illiberal rule” proposition. Further, we argue that Filipino voters are contingent supporters of illiberal politics while supporting the procedural principles of democracy at the baseline.
Comparison of the Accuracy of Pedicle Screw Placement Using a Fluoroscopy-Assisted Free-Hand Technique with Robotic-Assisted Navigation Using an O-Arm or 3D C-Arm in Scoliosis Surgery
Authors: Li Chao , Li Hao , Su Junxiao , Wang Zheng , Li Donglai , Tian Yonghao , Yuan Suomao , Wang Lianlei , Liu Xinyu
Published: December 2022

Study Design

Retrospective.

Objectives

To report and compare the application of robotic-assisted navigation with an O-arm or three-dimensional (3D) C-arm-assisted pedicle screw insertion in scoliosis surgery, and compare with free-hand technique.

Methods

One hundred and forty-four scoliosis patients were included in this study. Ninety-two patients underwent robotic-assisted pedicle screw insertion (Group A), and 52 patients underwent freehand fluoroscopy-guided pedicle screw insertion (Group B). Group A was further divided into Subgroup AI (n = 48; robotic-assisted navigation with an O-arm) and Subgroup AII (n = 44; robotic-assisted navigation with a 3D C-arm). The evaluated clinical outcomes were operation time, blood loss, radiation exposure, postoperative hospital stay, and postoperative complications. The clinical outcomes, coronal and sagittal scoliosis parameters and the accuracy of the pedicle screw placement were assessed.

Results

There were no significant differences in blood loss and postoperative hospital stay between Groups A and B ( P = .406, P = .138, respectively). Radiation exposure for patients in Group A (Subgroups AI or AII) was higher than that in Group B ( P < .005), and Subgroup AI had higher patient radiation exposure compared with Subgroup AII ( P < .005). The operation time in Subgroup AII was significantly longer than that in Subgroup AI and Group B ( P = .016, P = .032, respectively). The proportion of clinically acceptable screws was higher in Group A (Subgroups AI or AII) compared with Group B ( P < .005).

Conclusions

Robotic-assisted navigation with an O-arm or 3D C-arm effectively increased the accuracy and safety in scoliosis surgery. Compared with robotic-assisted navigation with a 3D C-arm, robotic-assisted navigation with an O-arm was more efficient intraoperatively.
Masked Speech Recognition by Normal-Hearing 6–13-Year-Olds in Conditions With and Without Interaural Difference Cues
Authors: Neher Tobias , Fogh Signe Hjorth , Koiek Shno
Published: December 2022

Using the Danish ‘børneDAT’ corpus, the current study aimed to (1) collect normative masked speech recognition data for 6–13-year-olds in conditions with and without interaural difference cues, (2) evaluate the test–retest reliability of these measurements, and (3) compare two widely used measures of binaural/spatial benefit in terms of the obtained scores. Seventy-four children and 17 young adults with normal hearing participated. Using headphone presentation, speech recognition thresholds (SRTs) were measured twice at two separate visits in four conditions. In the first two conditions, børneDAT sentences were presented in diotic stationary speech-shaped noise, with the sentences either interaurally in-phase (‘N0S0’) or interaurally out-of-phase (‘N0S180’). In the other two conditions, børneDAT sentences were simulated to come from 0° azimuth and two running speech maskers from either 0° azimuth (‘co-located’) or ±90° azimuth (‘spatially separated’). In relative terms, the children achieved lower SRTs in stationary noise than in competing speech, whereas the adults showed the opposite pattern. 12–13-year-old children achieved adult-like performance in all but the co-located condition. Younger children showed generally immature speech recognition abilities. Test–retest reliability was highest for the SRTs in stationary noise and lowest for the spatial benefit scores. Mean benefit was comparable for the two measures and participant groups, and the two sets of scores were not correlated with each other. Developmental effects were most pronounced in the conditions with interaural difference cues. In conclusion, reference data for the børneDAT corpus obtained under different acoustic conditions are available that can guide future research and potential clinical applications.
Intimate Partner Violence in Same-Sex Relationships: Are We Aware of the Implications?
Authors: Kar Anindya , Das Nabagata , Broadway-Horner Matt , Kumar Praveen
Published: December 2022

Intimate partner violence (IPV) has been a significant public health problem in same-sex relationships. However, health policies across the globe do not address IPV causing a massive gap in health and economic burden. In the last decade, crucial missing links have been established, and researchers tried to connect the dots of this severe health disparity. This intersectionality has found the impact of race, gender, class, physical ability, and legal framework of IPV in lesbian, gay, and bisexual (LGB) relationships. However, preventive strategies, training programs, and dialogues in the clinical field about IPV are from heteronormative lenses. This particular bias can perpetuate the issue and will remain one of the leading causes of health burden in the LGB population. This article reviews the lacunae in health policies regarding same-sex IPV, highlights its impact on minority mental health, and calls for attention to train health-care professionals regarding the same.
Sodium Valproate-induced Eosinophilic Exudative Pleural Effusion
Authors: Mohammed Saeed Rashaad , Mack Narine , Ramharack Kirk , Rampersad Jessica
Published: December 2022

A 34-year-old woman presented with a 3-day history of dyspnea. She denied any preceding fever, night sweats, cough, pleurisy, or coryzal symptoms. She was maintained on sodium valproate 800 mg b.i.d., phenytoin 100 mg o.d., folate 5 mg o.d., and clonazepam 2 mg nocte for a known seizure disorder. Clinical examination and radiologic imaging revealed a large left-sided pleural effusion with the associated collapse of the left lower lung lobe. A chest tube was inserted for diagnostic and therapeutic purposes and ≈500 mls of serous fluid was drained. The pleural fluid analysis confirmed an exudative pleural effusion. Extensive evaluation excluded known causes of exudative pleural effusion, and a diagnosis of sodium valproate-induced pleural effusion was made. Sodium valproate was tapered off and topiramate was added to the patient’s antiepileptic regimen. We recommend physicians be cognizant of sodium valproate-associated pleural effusion, even in the setting of chronic use.
Comprehensive Open Management of Buttock/Ischiofemoral Symptoms: The COMBIS Procedure for Posterior Hip Pain
Authors: Curley Andrew J. , Setliff Joshua C. , Greiner Justin J. , Keeling Laura E. , Mauro Craig S.
Published: December 2022

Background:

Posterior hip and buttock pain can arise from several overlapping but distinct etiologies. Ischiofemoral impingement, sciatic neuropathy, and proximal hamstring tendinopathy, occurring alone or in combination, have been implicated as precipitants. However, diagnosis and management of underlying pathology can be challenging, as few diagnostic modalities reliably differentiate between these etiologies and surgeon decision-making may be complicated by uncertainty over which pathology to address.

Indications:

Posterior hip and buttock pain which occurs in a sciatic nerve distribution and is refractory to conservative measures (eg, physical therapy, analgesics, and activity modification) raises suspicion for 1 or several of the above pathologies. A combined procedure to address all 3—ischiofemoral decompression, sciatic neurolysis, and proximal hamstring repair—is described here.

Technique Description:

The patient is placed prone on a radiolucent table. An incision is made, and dissection is taken down through the superficial layers of the buttock, gluteal fascia, and fascia overlying the proximal hamstring tendons. The sciatic nerve is identified, mobilized, and lysed using blunt dissection. The fascia overlying the ischium is incised and the tendinous insertion decorticated with rongeur. Two anchors are placed, and sutures are passed through the proximal hamstring tendon in mattress fashion. An incision is made in line with the external rotators and dissection is taken down to the lesser trochanter. The lesser trochanter is identified, and osteotomy performed, with mobilization and removal of the resected fragment. The interval in the external rotators is closed with interrupted suture.

Results:

This is an uncommon procedure with little data on patient outcomes. Nonetheless, it is effective for relief of symptoms related to the pathologies enumerated above. Keys to success include careful diagnosis and comfort with surgical technique.

Conclusion:

The COMBIS procedure simultaneously addresses 3 common etiologies of posterior hip and buttock pain. Although it is important to conduct a thorough diagnostic evaluation to rule out imitators, patients with symptoms due to ischiofemoral impingement, sciatic neuropathy, proximal hamstring tendinopathy, or combination thereof may experience good relief of symptoms with appropriate application of this technique. The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
Activation of the PP2A-B56α heterocomplex synergizes with venetoclax therapies in AML through BCL2 and MCL1 modulation
Authors: Peris Irene , Romero-Murillo Silvia , Martínez-Balsalobre Elena , Farrington Caroline C. , Arriazu Elena , Marcotegui Nerea , Jiménez-Muñoz Marta , Alburquerque-Prieto Cristina , Torres-López Andrea , Fresquet Vicente , Martínez-Climent Jose A. , Mateos Maria C. , Cayuela Maria L. , Narla Goutham , Odero Maria D. , Vicente Carmen
Published: December 2022

Venetoclax combination therapies are becoming the standard of care in acute myeloid leukemia (AML). However, the therapeutic benefit of these drugs in older/unfit patients is limited to only a few months, highlighting the need for more effective therapies. Protein phosphatase 2A (PP2A) is a tumor suppressor phosphatase with pleiotropic functions that becomes inactivated in ∼70% of AML cases. PP2A promotes cancer cell death by modulating the phosphorylation state in a variety of proteins along the mitochondrial apoptotic pathway. We therefore hypothesized that pharmacological PP2A reactivation could increase BCL2 dependency in AML cells and, thus, potentiate venetoclax–induced cell death. Here, by using 3 structurally distinct PP2A-activating drugs, we show that PP2A reactivation synergistically enhances venetoclax activity in AML cell lines, primary cells, and xenograft models. Through the use of gene editing tools and pharmacological approaches, we demonstrate that the observed therapeutic synergy relies on PP2A complexes containing the B56α regulatory subunit, of which expression dictates response to the combination therapy. Mechanistically, PP2A reactivation enhances venetoclax-driven apoptosis through simultaneous inhibition of antiapoptotic BCL2 and extracellular signal-regulated kinase signaling, with the latter decreasing MCL1 protein stability. Finally, PP2A targeting increases the efficacy of the clinically approved venetoclax and azacitidine combination in vitro, in primary cells, and in an AML patient-derived xenograft model. These preclinical results provide a scientific rationale for testing PP2A-activating drugs with venetoclax combinations in AML.
DDX41-associated susceptibility to myeloid neoplasms
Authors: Makishima Hideki , Bowman Teresa V. , Godley Lucy A.
Published: December 2022

Deleterious germ line DDX41 variants confer risk for myeloid neoplasms (MNs) and less frequently for lymphoid malignancies, with autosomal dominant inheritance and an estimated prevalence of 3% among MNs. Germ line DDX41 variants include truncating alleles that comprise about two-thirds of all alleles, missense variants located preferentially within the DEAD-box domain, and deletion variants. The identification of a truncating allele on tumor-based molecular profiling should prompt germ line genetic testing because >95% of such alleles are germ line. Somatic mutation of the wild-type DDX41 allele occurs in about half of MNs with germ line DDX41 alleles, typically in exons encoding the helicase domain and most frequently as R525H. Several aspects of deleterious germ line DDX41 alleles are noteworthy: (1) certain variants are common in particular populations, (2) MNs develop at older ages typical of de novo disease, challenging the paradigm that inherited cancer risk always causes disease in young people, (3) despite equal frequencies of these variants in men and women, men progress to MNs more frequently, suggesting a gender-specific effect on myeloid leukemogenesis, and (4) individuals with deleterious germ line DDX41 variants develop acute severe graft-versus-host disease after allogeneic hematopoietic cell transplantation with wild-type donors more than others unless they receive posttransplant cyclophosphamide, suggesting a proinflammatory milieu that stimulates donor-derived T cells. Biochemical studies and animal models have identified DDX41’s ability to interact with double-stranded DNA and RNA:DNA hybrids with roles in messenger RNA splicing, ribosomal RNAs or small nucleolar RNAs processing, and modulation of innate immunity, disruption of which could promote inflammation and drive tumorigenesis.
Elexacaftor/tezacaftor/ivacaftor corrects monocyte microbicidal deficiency in cystic fibrosis
Authors: Cavinato Luca , Luly Francesco R. , Pastore Valentina , Chiappetta Daniele , Sangiorgi Gloria , Ferrara Eva , Baiocchi Pia , Mandarello Giuseppe , Cimino Giuseppe , Del Porto Paola , Ascenzioni Fiorentina
Published: December 2022

Background

Cystic fibrosis (CF), which is caused by mutations in the CF transmembrane conductance regulator (CFTR), is characterised by chronic bacterial lung infection and inflammation. In CF, monocytes and monocyte-derived macrophages have been shown to display defective phagocytosis and antimicrobial activity against relevant lung pathogens, includingPseudomonas aeruginosa. Thus, we addressed the effect of CFTR triple modulator therapy (elexacaftor/tezacaftor/ivacaftor (ETI)) on the activity of CF monocytes againstP. aeruginosa.

Methods

Monocytes from people with CF (PWCF) before and after 1 and 6 months of ETI therapy were isolated from blood and infected withP. aeruginosato assess phagocytic activity and intracellular bacterial killing. The oxidative burst and interleukin-6 secretion were also determined. Monocytes from healthy controls were also included.

Results

Longitudinal analysis of the clinical parameters confirmed an improvement of lung function and lung microbiology by ETI. Both the phagocytic and microbicidal deficiencies of CF monocytes also improved significantly, although not completely. Furthermore, we measured an exuberant oxidative burst in CF monocytes before therapy, which was reduced considerably by ETI. This led to an improvement of reactive oxygen species-dependent bactericidal activity. Inflammatory response to bacterial stimuli was also lowered compared with pre-therapy.

Conclusions

PWCF on ETI therapy, in a real-life setting, in addition to clinical recovery, showed significant improvement in monocyte activity againstP. aeruginosa, which may have contributed to the overall effect of ETI on pulmonary disease. This also suggests that CF monocyte dysfunctions may be specifically targeted to ameliorate lung function in CF.
Respiratory effort during sleep and prevalent hypertension in obstructive sleep apnoea
Authors: Martinot Jean-Benoit , Le-Dong Nhat-Nam , Malhotra Atul , Pépin Jean-Louis
Published: December 2022

Background

Mechanisms underlying blood pressure changes in obstructive sleep apnoea (OSA) are incompletely understood. Increased respiratory effort is one of the main features of OSA and is associated with sympathetic overactivity, leading to increased vascular wall stiffness and remodelling. This study investigated associations between a new measure of respiratory effort (percentage of total sleep time spent with increased respiratory effort based on measurement of mandibular jaw movements (MJM): REMOV, %TST) and prevalent hypertension in adults referred for evaluation of suspected OSA.

Methods

A machine learning model was built to predict hypertension from clinical data, conventional polysomnography (PSG) indices and MJM-derived parameters (including REMOV). The model was evaluated in a training subset and a test subset.

Results

The analysis included 1127 patients: 901 (80%) in the training subset and 226 (20%) in the test subset. The prevalence of hypertension was 31% and 30%, respectively, in the training and test subsets. A risk stratification model based on 18 input features including REMOV had good accuracy for predicting prevalent hypertension (sensitivity 0.75 and specificity 0.83). Using the Shapley additive explanation method, REMOV was the best predictor of hypertension after clinical risk factors (age, sex, body mass index and neck circumference) and time with oxygen saturation <90%, ahead of standard PSG metrics (including the apnoea–hypopnoea index and oxygen desaturation index).

Conclusion

The proportion of sleep time spent with increased respiratory effort automatically derived from MJM was identified as a potential new reliable metric to predict prevalent hypertension in patients with OSA.
Epidemiological characteristics of nontuberculous mycobacteriosis and bronchiectasis: comparative study using national mortality statistics from 1970 to 2015 in Japan
Authors: Morimoto Kozo , Iwai Kazuro , Yoshiyama Takashi , Ito Masashi , Uesugi Fumiko , Asakura Takanori , Osawa Takeshi , Furuuchi Koji , Kurashima Atsuyuki , Fujiwara Keiji , Hasegawa Naoki , Tanaka Yoshiaki , Shoji Kudoh , Shiraishi Yuji , Mitarai Satoshi , Ato Manabu , Ohta Ken
Published: December 2022

Background

This study assessed longitudinal national data on mortality due to nontuberculous mycobacteriosis (NTMosis) and bronchiectasis and the association between the two diseases.

Methods

We analysed the national death statistics of Japan from 1970 to 2015. The International Classification of Disease (ICD) codes were used to extract the relevant data. Crude mortality, age-adjusted mortality and standardised mortality rates were calculated using vital statistics and the population in 2000. We also identified domestic publications related to NTMosis and bronchiectasis with an internet-based search system.

Results

The total number of bronchiectasis-related deaths remained at the same level, which was approximately 1000, for 45 years, although the number of deaths has consistently decreased in males but increased in females since the mid-1990s. A substantial increasing trend in females was also observed for NTMosis in the same period. The age-adjusted mortality data showed an increase in mortality in women due to NTMosis and confirmed the trend in bronchiectasis in women. The patterns in the number of domestic reports showed a recent slight increase in bronchiectasis and a marked increase in NTMosis.

Conclusions

The trends in bronchiectasis-related mortality differed by sex. The epidemiological trends in the two diseases were associated, especially in elderly females since the mid-1990s. It is suggested that pulmonary NTMosis without pre-existing bronchiectasis might be a leading cause of postinfectious bronchiectasis in Japan.
Expression of vasopressin and its receptors in migraine-related regions in CNS and the trigeminal system: influence of sex
Authors: Maddahi Aida , Edvinsson Lars , Warfvinge Karin
Published: December 2022

Background

Hypothalamus is a key region in migraine attacks. In addition, women are disproportionately affected by migraine. The calcitonin gene-related peptide (CGRP) system is an important key player in migraine pathophysiology. CGRP signaling could be a target of hormones that influence migraine. Our aim is to identify the expression of vasopressin and its receptors in the brain and in the trigeminovascular system with focus on the migraine-related regions and, furthermore, to examine the role of sex on the expression of neurohormones in the trigeminal ganglion.

Methods

Rat brain and trigeminal ganglia were carefully harvested, and protein and mRNA levels were analyzed by immunohistochemistry and real-time PCR, respectively.

Results

Vasopressin and its receptors immunoreactivity were found in migraine-related areas within the brain and, in the trigeminal ganglion, predominantly in neuronal cytoplasm. There were no differences in the number of positive immunoreactivity cells expression of CGRP and vasopressin in the trigeminal ganglion between male and female rats. In contrast, the number of RAMP1 (CGRP receptor), oxytocin (molecular relative to vasopressin), oxytocin receptor and vasopressin receptors (V1aR and V1bR) immunoreactive cells were higher in female compared to male rats. Vasopressin and its receptors mRNA were expressed in both hypothalamus and trigeminal ganglion; however, the vasopressin mRNA level was significantly higher in the hypothalamus.

Conclusions

A better understanding of potential hormonal influences on migraine mechanisms is needed to improve treatment of female migraineurs. It is intriguing that vasopressin is an output of hypothalamic neurons that influences areas associated with migraine. Therefore, vasopressin and the closely related oxytocin might be important hypothalamic components that contribute to migraine pathophysiology.
Utilisation of a mitochondrial intergenic region for species differentiation of fruit flies (Diptera: Tephritidae) in South Africa
Authors: Andrews Kelsey J , Bester Rachelle , Manrakhan Aruna , Maree Hans J
Published: December 2022

Background

Fruit flies (Diptera: Tephritidae) comprise species of agricultural and economic importance. Five such fruit fly species are known to affect commercial fruit production and export in South Africa:Ceratitis capitata,Ceratitis cosyra,Ceratitis rosa,Ceratitis quilicii, andBactrocera dorsalis. Management practices for these pests include monitoring, application of pest control products, post-harvest disinfestation measures and inspection of consignments both prior to shipment and at ports of entry. In activities relating to monitoring and inspection, accurate identification of these pests to species level is required. While morphological keys for adult stages of these fruit fly species have been well developed, morphological keys for earlier life stages remain problematic. In instances where closely related species cannot be reliably distinguished morphologically, there is a need for molecular tools to assist in identifying these five fruit fly species during surveillance practices, where sequencing-based approaches would be beneficial.

Results

Two complete mitochondrial genomes were assembled for each fruit fly species investigated using high throughput sequencing data generated in this study. A single primer set was designed to amplify a region between tRNAileand tRNAmet. The amplicon consists of a partial segment of tRNAile, intergenic region I (tRNAile- tRNAgln), the complete sequence of tRNAgln, intergenic region II (tRNAgln- tRNAmet), and a partial segment of tRNAmet. PCR amplicons were generated for 20 specimens of each species, five of which were colony adult males, five colony larvae, and 10 wild, trap-collected specimens. Upon analysis of the amplicon, intergenic region I was identified as the most informative region, allowing for unambiguous identification of the five fruit fly species. The similarity in intergenic region II was too high betweenC. rosaandC. quiliciifor accurate differentiation of these species.

Conclusion

The identity of all five fruit flies investigated in this study can be determined through sequence analysis of the mitochondrial intergenic regions. Within the target amplicon, intergenic region I (tRNAile- tRNAgln) shows interspecific variation sufficient for species differentiation based on multiple sequence alignment. The variation in the length of intergenic region I is proposed as a potential tool for accurately identifying these five fruit flies in South Africa.