bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluid intelligence but not need for cognition is associated with attitude change in response to the correction of misinformation
Authors: Hutmacher Fabian , Appel Markus , Schätzlein Benjamin , Mengelkamp Christoph
Published: September 2024

Misinformation can profoundly impact an individual’s attitudes—sometimes even after the misinformation has been corrected. In two preregistered experiments (N1 = 355, N2 = 725), we investigated whether individual differences in the ability and motivation to process information thoroughly influence the impact of misinformation in a news media context. More specifically, we tested whether fluid intelligence and need for cognition predicted the degree to which individuals who were exposed to misinformation changed their attitudes after receiving a correction message. We found consistent evidence that higher fluid intelligence is associated with a more pronounced correction effect, while need for cognition did not have a significant effect. This suggests that integrating a correction message with a previously encountered piece of misinformation can be challenging and that correction messages consequently need to be communicated in a way that is accessible to a broad audience.
Investigating patellar motion using weight-bearing dynamic CT: normative values and morphological considerations for healthy volunteers
Authors: Buzzatti Luca , Keelson Benyameen , Héréus Savanah , Van den Broeck Jona , Scheerlinck Thierry , Van Gompel Gert , Vandemeulebroucke Jef , De Mey Johan , Buls Nico , Cattrysse Erik
Published: September 2024

Background

Patellar instability is a well-known pathology in which kinematics can be investigated using metrics such as tibial tuberosity tracheal groove (TTTG), the bisect offset (BO), and the lateral patellar tilt (LPT). We used dynamic computed tomography (CT) to investigate the patellar motion of healthy subjects in weight-bearing conditions to provide normative values for TTTG, BO, and LPT, as well as to define whether BO and LPT are affected by the morphology of the trochlear groove.

Methods

Dynamic scanning was used to acquire images during weight-bearing in 21 adult healthy volunteers. TTTG, BO, and LPT metrics were computed between 0° and 30° of knee flexion. Sulcus angle, sulcus depth, and lateral trochlear inclination were calculated and used with the TTTG for simple linear regression models.

Results

All metrics gradually decreased during eccentric movement (TTTG, -6.9 mm; BO, -12.6%; LPT, -4.3°). No significant differences were observed between eccentric and concentric phases at any flexion angle for all metrics. Linear regression between kinematic metrics towards full extension showed a moderate fit between BO and TTTG (R2 0.60, β 1.75) and BO and LPT (R2 0.59, β 1.49), and a low fit between TTTG and LPT (R2 0.38, β 0.53). A high impact of the TTTG distance over BO was shown in male participants (R2 0.71, β 1.89) and patella alta individuals (R2 0.55, β 1.91).

Conclusion

We provided preliminary normative values of three common metrics during weight-bearing dynamic CT and showed the substantial impact of lateralisation of the patella tendon over patella displacement.

Relevance statement

These normative values can be used by clinicians when evaluating knee patients using TTTG, BO, and LPT metrics. The lateralisation of the patellar tendon in subjects with patella alta or in males significantly impacts the lateral displacement of the patella.

Key Points

Trochlear groove morphology had no substantial impact on motion prediction.

The lateralisation of the patellar tendon seems a strong predictor of lateral displacement of the patella in male participants.

Participants with patella alta displayed a strong fit between the patellar lateral displacement and tilt.

TTTG, BO, and LPT decreased during concentric movement.

Concentric and eccentric phases did not show differences for all metrics.

Graphical Abstract
Development of a questionnaire to assess the patient perspective regarding challenges in psoriatic arthritis treatment—a mixed-methods study
Authors: Lucas Ribeiro André , Tessari Júlia Andressa , Lubianca Kohem Charles , Esther Palominos Penélope , Mendonça da Silva Chakr Rafael
Published: September 2024

Background

Limited data exist on psoriatic arthritis (PsA) treatment in lower-income regions, particularly from the patient perspective. This study explores the challenges faced by socioeconomically vulnerable PsA patients and the reasons for non-adherence to treatment guidelines. The main objective of the study is to develop a questionnaire to identify the primary challenges in PsA treatment adherence and to analyze its feasibility while simultaneously understanding the target population’s unique characteristics.

Methods

We included PsA patients meeting the Classification Criteria for PsA (CASPAR), excluding those with other overlapping inflammatory diseases. The study, supported by two patient-research partners, began with focus groups to identify treatment challenges, leading to the creation of a 26-item questionnaire. Its reliability was verified using the test-retest method, targeting a percent agreement ≥ 0.8. Then, PsA patients at a rheumatology clinic completed the final survey.

Results

The study involved 69 PsA patients. The final questionnaire contained 26-questions across five-domains, with a 92.2% agreement rate and an average completion time of 8.3 minutes. Diagnostic delays exceeded a year for 59% of patients and more than two years for 33%. Daily life disruptions affected 43.2% of patients, with 35.3% taking sick leave or retiring. Around 25% waited over 8 weeks for drug approval, and 17.6% required legal intervention to access medication. Drug dispensation issues impacted about 60% of patients. Furthermore, 66.7% lived far from their rheumatologist, with 49% traveling over an hour for appointments. Approximately 30% were unaware of the risks of methotrexatein relation to alcohol consumption and pregnancy.

Conclusions

The questionnaire was feasible and reliable, with its results underscoring patient-centric challenges in PsA management, particularly concerning diagnostic delays and medication access, as well as daily life disruptions and misinformation. These findings emphasize the urgency for healthcare reforms aimed at improving diagnosis efficiency, patient education, and streamlined medication access, emphasizing the need for tailored initiatives to improve the healthcare experience for PsA patients.
Ultrasound-guided combined intra-articular corticosteroids injection and suprascapular nerve block for pain control in patients with frozen shoulder
Authors: Shaaban Ebraheem Hassan Abubakr , El Shafei Mohamed Mahmoud , El Desouki Salah El Deen , Elnemr Rehab , Ezz Eldin Omnia
Published: September 2024

Background

Frozen shoulder is an incapacitating disease that causes pain and limitation in the shoulder joint functional capacity. This work aimed to assess the efficacy of ultrasound-guided combined intra-articular corticosteroids (CS) injection and suprascapular nerve block (SSNB) in pain control in patients with frozen shoulders.

Results

Our prospective study included 40 patients, equally divided into two groups: group A; managed with combined ultrasound (US) guided intra-articular corticosteroids injection (IACSI) and SSNB, and group B patients managed with US-guided SSNB. The visual analog scale score statistically significantly improved after both injections. This success was maintained and showed mild improvement at 8-week intervals (with increased patient capability to do physiotherapy after pain control). Similarly, improvement in the functional capacity of the shoulder joint was identified and assessed by the Oxford shoulder score (OSS) in both groups. Mean OSS was statistically significantly higher at 4-week intervals than before the nerve block for groups A and B. At 8 weeks interval, this favorable result was sustained (p < .001).

Conclusions

US-guided SSNB is an effective, radiation-free method to alleviate frozen shoulder-related pains. However, US-guided combined SSNB and IACSI was more effective than SSNB alone in both pain alleviation and improved shoulder joint function.
Estimation of isoniazid by digital image colorimetry: an integration of green chemistry and smartphone technology
Authors: Yenduri Suvarna , Prashant K. Naga
Published: September 2024

Background

This study proposes a simple digital image colorimetric method using a smartphone for the quantitative analysis of isoniazid in pharmaceutical medications. The analytical methodology employed in this study involved the utilization of the reaction between isoniazid and FC reagent under alkaline conditions. The chemical reaction led to the creation of a complex with a blue-gray color, exhibiting a peak absorption at a wavelength of 760 nm. An Android application was employed to perform a smartphone-based determination based on separating the captured color into different color channels such as red, blue, green, etc. The experimental procedure involved the utilization of three smartphones for the determination, which was subsequently followed by a comparative analysis of the results obtained from these devices using spectrophotometric measurements.

Results

The B channel had the highest level of optimization in terms of analytical parameters. The limits of detection (LOD) were 0.586, 2.478, and 1.396 µg/ml for S1, S2, and S3, respectively, and for the spectrophotometer, it was found to be 0.416 µg/ml. Similarly, LOQs were determined as 1.673, 7.511, 4.232, and 1.302 µg/ml. A %RSD of 1.3 for precision and an LOD of 0.013 g dm−3 were obtained for the spectroscopic method. The % recovery in the accuracy study was found to be 99.69, 101.804, 109.28, and 100.13 for S1, S2, S3, and spectrophotometer, respectively.

Conclusion

The colorimetric results from smartphone application are similar to those from spectrophotometric analyses.
Trypsin, chymotrypsin and elastase in health and disease
Authors: Famutimi Oladoyin Grace , Adebiyi Victor Gbolahan , Akinmolu Bukola Grace , Dada Omoniyi Vincent , Adewale Isaac Olusanjo
Published: September 2024

Background

Serine proteases represent over 1% of all proteins in humans. This family of proteins is found on cell surfaces, subcellular organelles like lysosomes or mitochondria, within the nucleus and the protoplasm.

Main body of the abstract

Among them, trypsin, chymotrypsin and elastase have aroused great interest because of their numerous functions in pathophysiological processes. Altered expression of these enzymes in experimental animal models and humans has been related to various pathologies, like developmental defects, metabolic dysfunctions, cancer, peripheral vascular diseases and infectious diseases. Trypsin and chymotrypsin-like proteases activate, or less oftentimes inactivate, numerous substrates, together with growth factors, receptors, adhesion molecules, angiogenic factors and metalloproteases. Among these substrates, a number of them are key factors in cancer progression, metastasis and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease. Elastin-degrading enzyme- elastase, slowly damages elastin over the lifetime of an organism. The physiological processes triggered by elastase leads to the progression of different conditions such as cancer, metabolic syndrome, pulmonary emphysema, atherosclerosis, and chronic obstructive pulmonary disease. These serine proteases are currently considered to be targets for the development of new potent therapeutics.

Short conclusion

The cumulative knowledge that outlined the physiological functions and pathological implications of these proteases and the proposed strategies to regulate a number of their activities and their targeting for therapeutic application and validation in selected disease states are highlighted. These should enhance our appreciation of their roles in aetiology of some diseases as well as the chemotherapeutic benefits of their inhibition or modulation.
Clinical factors associated with bone mineral density among individuals with osteoarthritis of the hip and/or knee: a systematic review
Authors: Adekanla Babatunde A. , Mbada Chidozie E. , Idowu Opeyemi A. , Ademoyegun Adekola A. , Onigbinde Omotola A. , Fawole Henrietta O. , Afolabi Joshua , Adeniji Tolulope , Akinpelu Aderonke O.
Published: September 2024

Background and objective

The association of clinical factors of osteoarthritis (OA) with bone mineral density (BMD) is not well understood. We aimed to synthesize evidence regarding the associated clinical factors for low BMD in people with knee and/or hip osteoarthritis.

Methods

A systematic literature search limited to human studies was conducted from inception to September 12, 2022. CINAHL, Cochrane, Medline, PsycINFO, PubMed, Web of Science, and African Journal online databases were searched for all clinical factors associated with low BMD (either as osteopenia or osteoporosis). Gray literature or abstracts or protocols, studies with a mixed population of OA without a subgroup analysis for hip and or KOA and non-English were excluded. Following the title and abstract, full-text, screenings, and data extraction, data from eligible studies were synthesized based on the main objective of the study. The Joanna Brigg’s Institute (JBI) Critical Assessment tool was used for quality appraisal. Narrative synthesis and best evidence synthesis were used in the study.

Result

Five studies (2 case–control, 3 cross-sectional) were included after screening 3355 titles and abstracts. Clinical factors reported in the five studies included: body mass index (BMI); pain, function, and stiffness; symptom duration; presence of varus/valgus deformity; quality of life; and knee function. Whilst there was limited evidence to support the association between BMD measured at any site of the body and BMI, as well as conflicting evidence for the association of BMD with age and gender, there was insufficient evidence to support the association of BMD with other identified clinical factors of hip and or/ knee OA (p < 0.05). In addition, there is conflicting evidence for the association between BMD measured at the lumbar spine and BMI.

Conclusion

There is insufficient evidence on the association between BMD and its associated clinical factors. With the attendant likelihood of bias in existing studies, there is a need for well-designed studies on bone health in OA.
Vocal dysfunction following thyroid surgery: a multidimensional subjective and objective study
Authors: Aref Essam Eldin Mohamed , Ahmed Gamal Abd El-Hamed , Ibrahim Reham AbdEl-Wakil , Shrkawy Aya Essam
Published: September 2024

Background and objective

Following thyroid surgery, vocal changes are a common complication and well-known morbidity that may be linked to neuronal and non-neuronal voice breakdown. Nevertheless, their effects on different voice characteristics are not fully understood, and their bases are still poorly characterized. In order to determine the diagnostic indicators that address the nature of such post-thyroidectomy voice alternations, this study was designed to provide a multidimensional assessment of vocal function after thyroid surgery.

Methods

This research was a 1-year prospective cohort study conducted on 100 adult patients aged 40.19 (± 12.82) years who were recruited from the outpatient clinic of Phoniatric Unit, Assiut University Hospital, and scheduled to undergo thyroid surgery during the period from November 2020 to November 2021. All subjects underwent vocal assessment preoperatively and 15 days, 1 month, and 2 months postoperatively by filled in subjective evaluation of voice complaints via voice handicap index (VHI-30), auditory perceptual assessment (APA) of the voice, and videolaryngoscopy in addition to acoustic analysis using computerized speech lab (CSL). Statistical analysis was performed to compare multi-parameter voice assessment tools across different assessment time points.

Results

The voice changes were significantly decreased from 51.0% after 15 days postoperatively to 33.0% after 2 months of follow-up. Among these cases, 35.0% cases developed vocal fold paralysis and complained of a breathy voice (27% developed unilateral vocal fold paralysis, and 8% developed bilateral focal fold lesions), and the remaining 16.0% cases had no paralytic manifestations. Also, only one case developed gross lesion “bilateral vocal fold nodules.” The subjective evaluation of voice outcome after thyroidectomy showed significant improvement in VHI subscales and total score from 15 days postoperatively to 2 months of follow-up (P < 0.001). All of the acoustic parameters except HNR showed a significant difference across the different assessment settings (P < 0.001).

Conclusion

Thyroidectomy can result in significant vocal alterations, even in cases where the laryngeal nerve is unharmed. These changes should be taken into consideration in patient having thyroid surgery, especially a total thyroidectomy because of malignant lesions. More efforts are needed in order to determine the extent and pathophysiological reasons for the vocal alterations following thyroid surgery in order to reduce the morbidity associated with one of the most popular surgical procedures performed globally.
Dysgeusia and paresthesia following suspension microlaryngoscopy: review and recommendations for risk reduction
Authors: Al-Yahya Syarifah Nafisah , Rahim Norazila Abdul , Kailani Abdul Azim Al-Abrar Ahmad , Sobani Muhamad Ariff , Mansor Masaany
Published: September 2024

Background

Dysgeusia or altered taste is a rare complication following suspension microlaryngoscopy with the incidence ranging from 2.9 to 12.1%. We report this with recommendations to avoid similar complications following suspension laryngoscopy, tonsillectomy, and tongue base surgery which require pressure to be placed on the tongue for better surgical field visualization.

Case presentation

A 53-year-old man with underlying diabetes mellitus presented with long standing history of irritative cough, globus sensation, and evidence of laryngopharyngeal reflux. A left ventricle swelling was noted on flexible laryngoscopy and neck. He underwent direct laryngoscopy and biopsy of the left ventricle lesion which revealed to be acute on chronic inflammation. Day 1 postoperatively, patient complained of reduced sensation over left hemi-tongue. A referral to a neurologist was made for further examination and he was found to have loss of taste over anterior two-third of tongue and treated with vitamin B complex. To date, dysgeusia remains persistent. Patient relayed his grievances to the hospital following these complications. Review of literature on relevant topic was made through PubMed, Web of Science, and Cochrane Library Database by two reviewers, working independently. Twenty-three papers, available in full, written in English language, containing number of cases, type of surgery, and complications were extracted and studied.

Conclusions

Risk of dysgeusia and paresthesia postoperatively should be informed during consent taking for all patients undergoing tonsillectomy, laryngeal microsurgery, and tongue base surgery. Zinc deficiency should be investigated in patients with persistent taste disturbance post-tonsillectomy. Intermittent release during suspension laryngoscopy beyond 30 min to reduce post-surgical complications. Greater care should be taken to reduce the amount of force during the suspension laryngoscopy due to smaller oral and oropharyngeal structure in female. Keeping close to the tonsillar capsule particularly in mid and lower pole areas should be done in tonsillectomy using diathermy dissection.
Severity, mortality, and incidence of venous thromboembolism in COVID-19 patients
Authors: Ali Ahmed Al-Husseiny , Assal Hebatallah Hany , Ismail Mohamed Said , Mashaly Basem Abdelmonem , Elwafa Gihan Saad Abo
Published: September 2024

Background

COVID-19 is a global pandemic that negatively affected the world economy and the health care resources. It is associated with great health impact, mortality, and long-term sequelae.

Methods

History taking computed tomography of the chest and laboratory investigations including complete blood count, liver and kidney function tests, serum ferritin, C-reactive protein, and D-dimer were done.

Results

A total of 246 hospitalized COVID-19 patients were enrolled. Male predominance (67.1% of the total study population) was observed. The mean age was 57.26 ± 14.08 years. Moderate cases comprised 63.8% of the total study population, 22.4% were severe cases, and 13.8% were critical cases. The mortality rate was 8.13% and 6.1% developed venous thromboembolism.

Conclusion

Age, smoking, and the presence of previous pulmonary disease were among the most important factors affecting COVID-19 severity. The severity of the disease greatly influences the incidence of venous thromboembolism and the outcome of the disease.
Legislation and policy for involuntary mental healthcare across countries in the FOSTREN network: rationale, development of mapping survey and protocol
Authors: Aluh Deborah Oyine , Lantta Tella , Lourenço Tânia , Birkeland Søren Fryd , Castelpietra Giulio , Dedovic Jovo , Caldas-de-Almeida José Miguel , Rugkåsa Jorun
Published: September 2024

Background

Several countries are currently revising or have already revised their mental health laws to align with the global movement to reduce the use of coercive care. No government has yet fully implemented the recommendation of the United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) to eliminate the use of coercion in mental healthcare. Consequently, the international field of mental health law and policy is in a degree of flux.

Aims

To describe the rationale, development and protocol for a project that will map and examine how mental health laws, policies and service capacity across European countries relate to the use of coercive measures, including involuntary admissions and treatment, restraints and seclusion. This will help to better understand the current situation and explore future directions of policies regarding coercive care.

Method

The project is being carried out under the purview of the European Cooperation in Science and Technology (COST) action network, entitled FOSTREN (Fostering and Strengthening Approaches to Reducing Coercion in European Mental Health Services). A multidisciplinary group of experts developed a comprehensive survey assessing mental health laws, policies and service frameworks, based on World Health Organization and UNCRPD recommendations. The survey was piloted in three countries, revised and disseminated to 30 FOSTREN country representatives. The survey will provide data for three strands of work on legislation, policies and service-level context. A comprehensive evaluation will be conducted, drawing on findings from all work packages.

Conclusions

The project could inform the development of strategies, interventions and legislation to address gaps and promote compliance with international standards.
Development and Optimization of a Bladder Cancer Algorithm Using SEER-Medicare Claims Data
Authors: Gore John L. , Wright Phoebe , Shih Vanessa , Chang Nancy N. , Noshad Sina , Rey Gabriel G. , Wang Steven , Narayanan Sujata
Published: September 2024

PURPOSE

Categorizing patients with cancer by their disease stage can be an important tool when conducting administrative claims-based studies. As claims databases frequently do not capture this information, algorithms are increasingly used to define disease stage. To our knowledge, to date, no study has used an algorithm to categorize patients with bladder cancer (BC) by disease stage (non–muscle-invasive BC [NMIBC], muscle-invasive BC [MIBC], or locally advanced/metastatic urothelial carcinoma [la/mUC]) in a US-based health care claims database.

METHODS

A claims-based algorithm was developed to categorize patients by disease stage on the basis of the administrative claims portion of the SEER-Medicare linked data. The algorithm was validated against a reference SEER registry, and the algorithm's parameters were iteratively modified to improve its performance. Patients were included if they had an initial diagnosis of BC between January 2016 and December 2017 recorded in SEER registry data. Medicare claims data were available for these patients until December 31, 2019. The algorithm was evaluated by assessing percentage agreement, Cohen's kappa (κ), specificity, positive predictive value (PPV), and negative predictive value (NPV) against the SEER categorization.

RESULTS

A total of 15,484 patients with SEER-confirmed BC were included: 10,991 (71.0%) with NMIBC, 3,645 (23.5%) with MIBC, and 848 (5.5%) with la/mUC. After multiple rounds of algorithm optimization, the final algorithm had an agreement of 82.5% with SEER, with a κ of 0.58, a PPV of 87.0% for NMIBC, and 76.8% for MIBC and a high NPV for la/mUC of 98.0%.

CONCLUSION

This claims-based algorithm could be a useful approach for researchers conducting claims-based studies categorizing patients with BC at diagnosis.
PEARL: A Phase Ib/II Biomarker Study of Adding Radiation Therapy to Pembrolizumab Before Neoadjuvant Chemotherapy in Human Epidermal Growth Factor Receptor 2–Negative Breast Cancer
Authors: Ho Alice Y. , Shiao Stephen , Kobald Samantha A. , Chen Jonathan , Duda Dan G. , Ly Amy , Bossuyt Veerle , Cho Hae Lin , Arnold Brittany , Knott Simon , Gupta Gaorav P. , McAndrew Philomena , Karlan Scott , Tighiouart Mourad , Muzikansky Alona , Basho Reva , McArthur Heather
Published: September 2024

PURPOSE

To assess safety and immune biomarkers after preoperative radiation therapy (RT) and anti-PD1 therapy in breast cancer.

MATERIALS AND METHODS

A phase I/IIb trial of pembrolizumab with RT was conducted in patients with triple-negative breast cancer (TNBC) and hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) breast cancer. All received pembrolizumab followed by a second cycle + RT (anti-PD1/RT) of 24 Gy/three daily fractions delivered to the breast tumor and then neoadjuvant chemotherapy (NAC). Blood and tumor biopsies were obtained at baseline, after anti-PD1, and after anti–PD-RT. Coprimary end points were safety and change in tumor-infiltrating lymphocytes (TILs). Secondary end points were pathologic complete response (pCR), residual cancer burden (RCB) rates, and event-free survival (EFS).

RESULTS

Sixty-six patients with stage I-III breast cancer (54 TNBC, 12 HR+/HER2–) were enrolled. The median follow-up was 32 months. Safety end point was met. Incidence of grade ≥3 toxicities was 41%. The pCR rate was 59.2%, 33.3%, and 54.5% for the TNBC, HR+/HER2–, and entire cohort, respectively. A total of 77.8% of TNBC and 41.6% of HR+/HER2– had a near pCR (RCB 0-1). The 3-year EFS was 80%. In the entire cohort, PD-L1 expression increased after anti-PD1 (median Combined Positive Score [CPS], 7.49-23.20; 95% CI, –41.88 to –6.30;
P
= .044) and anti-PD1/RT (median CPS, 7.49-23.41; 95% CI, –41.88 to –6.30;
P
= .009), compared with baseline. In TNBC, adding RT to anti-PD1 significantly decreased TILs (28.9%-17.1%; 95% CI, 2.46 to 21.09;
P
= .014). Baseline TILs correlated with PD-L1 expression and TNF-a.

CONCLUSION

Preoperative RT with pembrolizumab is safe and results in high pCR rates and 3-year EFS, despite the lack of pembrolizumab during NAC. PD-L1 and TILs may be predictive biomarkers for preoperative anti-PD1/RT response. Reduction in TILs after adding RT to anti-PD1 highlights the importance of treatment sequencing.
Palbociclib in Solid Tumor Patients With Genomic Alterations in the cyclinD-cdk4/6-INK4a-Rb Pathway: Results From National Cancer Institute-Children's Oncology Group Pediatric Molecular Analysis for Therapy Choice Trial Arm I (APEC1621I)
Authors: Macy Margaret E. , Mody Rajen , Reid Joel M. , Piao Jin , Saguilig Lauren , Alonzo Todd A. , Berg Stacey L. , Fox Elizabeth , Weigel Brenda J. , Hawkins Douglas S. , Mooney Margaret M. , Williams P. Mickey , Patton David R. , Coffey Brent D. , Roy-Chowdhuri Sinchita , Takebe Naoko , Tricoli James V. , Janeway Katherine A. , Seibel Nita L. , Parsons D. Williams
Published: September 2024

PURPOSE

The National Cancer Institute-Children's Oncology Group Pediatric Molecular Analysis for Therapy Choice trial assigned patients age 1-21 years with relapsed or refractory solid tumors, lymphomas, and histiocytic disorders to phase II treatment arms of molecularly targeted therapies on the basis of genetic alterations detected in their tumor. Patients with tumors that harbored prespecified genomic alterations in the cyclinD-CDK4/6-INK4a-Rb pathway with intact Rb expression were assigned and treated with the cdk4/6 inhibitor palbociclib.

METHODS

Patients received palbociclib orally once daily for 21 days of 28-day cycles until disease progression, intolerable toxicity, or up to 2 years. The primary end point was objective response rate; secondary end points included safety/tolerability and progression-free survival.

RESULTS

Twenty-three patients (median age, 15 years; range, 8-21) were enrolled; 20 received protocol therapy and were evaluable for toxicity and response. Of the evaluable patients, the most common diagnoses were osteosarcoma (n = 9) and rhabdomyosarcoma (n = 6). A single actionable gene amplification was found in 19 tumors ( CDK4, n = 11, CDK6, n = 2, CCND3, n = 6), with one tumor harboring two amplifications ( CDK4 and CCND2). Hematologic toxicities were the most common treatment-related events. No objective responses were seen. Two patients with tumors harboring CDK4 amplifications (neuroblastoma and sarcoma) had best response of stable disease for six and three cycles. Six-month progression was 10% (95% CI, 1.7 to 27.2).

CONCLUSION

The CDK4/6 inhibitor palbociclib at 75 mg/m2 orally daily was tolerable in this heavily pretreated cohort. No objective responses were observed in this histology-agnostic biomarker-selected population with treatment-refractory solid tumors, demonstrating that pathway alteration alone is insufficient in pediatric cancers to generate a response to palbociclib monotherapy.
Pituitary Apoplexy: Comorbidities, Management, and Outcomes—A Spanish Observational Multicenter Study
Authors: Biagetti Betina , Cordero Asanza Esteban , Pérez-López Carlos , Araujo-Castro Marta , Camara Rosa , Guerrero-Pérez Fernando , Vicente Almudena , Lamas Cristina , Serra Guillermo , Echarri Ana Irigaray , Ollero M Dolores , González Molero Inmaculada , Villar-Taibo Rocío , Moure Rodríguez María Dolores , García-Feijoo Pablo , Berrocal Víctor Rodríguez , Sánchez Ramirez María Noelia , Gutiéerrez Hurtado Alba , Capristan-Díaz Vanessa , Simó-Servat Andreu , Gallach Marta , Safont Perez Eva , González Rosa Victoria , Civantos Soralla , Asensio-Wandosell Diego , Martinez-Saez Elena , Menéndez Torre Edelmiro , Aulinas Anna , Iglesias Pedro , Diez Juan J , Bernabéu Ignacio , Álvarez-Escolá Cristina , Puig-Domingo Manel
Published: September 2024

Background

Pituitary apoplexy (PA) is the paradigm of endocrine and neurosurgical emergency.

Objective

To evaluate the comorbidities, risk factors, clinical presentation, pituitary apoplexy score (PAS), and the outcomes of surgical vs conservative management of PA in Spain.

Methods

Spanish multicenter, observational study of 301 patients with acute PA. Statistical analyses compared risk factors, clinical presentation, and outcomes between surgical and conservative treatment groups, adjusting for potential confounders. The prevalence of cardiovascular risk factors in patients with PA was compared with the Spanish population and with patients with nonfunctioning pituitary adenomas.

Results

Median age was 59.3 years, 201 (66.8%) were men; nonfunctioning adenomas (77.9%) were the most common tumor type. The prevalence of diabetes (20.3% vs 13.9%, P < .01), hypertension (48.8% vs 33.4%, P < .01), and dyslipidemia (44.2% vs 23.3%, P < .01), exceeded the Spanish age-adjusted population prevalence. Overall, 209 (69.4%) underwent surgery and 92 (30.6%) received conservative treatment. Surgical patients had larger tumors (26.2 vs 21.0 mm, P < .01), more frequent chiasmal compression (77.2% vs 53.4%, P < .01), and higher values of PAS. In the follow-up, although there were no statistically significant differences in anterior pituitary hormonal deficits between treatments, permanent vasopressin deficiency was more frequent after surgery (14.8% vs 3.3%, P < .01).

Conclusions

There is a high burden of cardiovascular risk factors among patients with PA, suggesting that metabolic factors may play a potential role in the development of PA. This underscores the need for comprehensive management of these conditions in addition to treating the apoplexy itself in this population. Surgical management has a relevant place in PA approach mainly in patients with higher PAS. However, it leads a permanent vasopressin deficit more frequently than a conservative approach.
Plasma Endocannabinoids Are Independently Associated With the Metabolic Function of White Adipose Tissue
Authors: Dion Dany , Noll Christophe , Fortin Mélanie , Haroune Lounès , Saibi Sabrina , Sarret Philippe , Carpentier André C
Published: September 2024

Context

Little is known about the link between the endocannabinoid (EC) system and the in vivo metabolic function of white adipose tissue (WAT).

Objective

We aimed to evaluate whether ECs are linked to postprandial fatty acid metabolism and WAT metabolic function.

Methods

Men and women, with (IGT, n = 20) or without impaired glucose tolerance (NGT, n = 20) underwent meal testing with oral and intravenous stable isotope palmitate tracers and positron emission tomography with intravenous [11C]-palmitate and oral [18F]-fluoro-thia-heptadecanoic acid to determine systemic and organ-specific dietary fatty acid (DFA) and nonesterified fatty acid (NEFA) metabolism and partitioning. We determined fasting and postprandial plasma levels of EC by ultra-high performance liquid chromatography–tandem mass spectrometry.

Results

All ECs of the 2-monoacylglycerol (2-MAG) family displayed a progressive postprandial increase up to 360 minutes after meal intake that was more pronounced in women with IGT. N-acylethanolamine (NAE) levels decreased between fasting and 180 minutes, followed by a return to preprandial values at 360 minutes and were also increased in women with IGT. Postprandial area under the curve (AUC) of palmitate appearance rate was significantly and independently associated with postprandial AUC of anandamide (AEA; P = .0003) and total energy expenditure (P = .0009). DFA storage in abdominal subcutaneous adipose tissue was positively predicted by fasting 2-arachidonoylglycerol (2-AG; P < .04).

Conclusion

EC levels of the NAE family independently follow plasma NEFA metabolism, whereas 2-MAG closely follow the spillover of triglyceride-rich lipoprotein intravascular lipolytic products. Whether these associations are causal requires further investigation.
A Year at the Forefront of Streptophyte Algal Evolution
Authors: Bowles Alexander M. C.
Published: September 2024

Land plants originated from an algal ancestor ∼500 million years ago in one of the most important evolutionary events for life on Earth. Extant streptophyte algae, their closest living relatives, have subsequently received much attention to better understand this major evolutionary transition. Streptophyte algae occupy many different environments, have diverse genomes and display contrasting morphologies (e.g. unicellular, filamentous, three-dimensional). This has historically made inferring these evolutionary events challenging. This A Year at the Forefront Review focusses on research published between July 2023 and June 2024 and intends to provide a short overview of recent discoveries, innovations, resources, and hypotheses regarding streptophyte algal evolution. This work has provided mechanistic insights into ancient evolutionary events that prefigured the origin of land plants and raises new questions for future research into streptophyte algae.
The contractile efficiency of the mantle muscle of European common cuttlefish (Sepia officinalis) during cyclical contractions
Authors: Gladman Nicholas W. , Askew Graham N.
Published: September 2024

Escape jet propulsion swimming in cuttlefish (Sepia officinalis) is powered by the circular muscles surrounding the mantle cavity. This mode of locomotion is energetically costly compared with undulatory swimming. The energetic cost of swimming is determined by the mechanical power requirements and the efficiency with which chemical energy is transferred into useful mechanical work. One step in this energy transduction process is the transfer of energy from ATP hydrolysis into mechanical work by the muscles. Here, we determined the efficiency of this step, termed the contractile efficiency. Muscle preparations from the circular muscles of the mantle cavity were subjected to sinusoidal length changes at different cycle frequencies, and stimulated with a phase and duration that maximised initial net work. Changes in ATP, arginine phosphate and octopine content between control and exercised muscles were determined and used to calculate the energy released from ATP hydrolysis (Emet). The maximum contractile efficiency (the ratio of net work to Emet) was 0.37, occurring at the same cycle frequency at which mechanical power was maximal and that was used during jet propulsion swimming, suggesting that cuttlefish muscle is adapted to generate muscular power efficiently. The overall efficiency of cuttlefish jet propulsion swimming was estimated to be 0.17, which is broadly comparable to that measured during animal flight and human-powered pedalled locomotion, indicating the high energetic costs of jet propulsion swimming are not due to inefficient locomotion per se; instead, they result from the relatively high mechanical power requirements.
Examining the relationship between health literacy and pesticide protective behaviors among farmers in Thailand
Authors: Rachutorn Thiwakorn , Aeksanti Thawatchai , Pall Chamroen , Tanamool Varavut , Srisuwan Anake , Mok Somany , S Dewey Rebecca , Sim Samphors , Kong Malika , Vong Pisey
Published: September 2024

Background The use of chemical pesticides without proper health literacy (HL) and necessary pesticide protective behaviors (PPB) can result in adverse effects on human health. Methods This study aims to determine if there is a correlation between HL and PPB among farmers in the Nakhon Ratchasima province, using a random sample of 464 farmers. Structured interviews consisted of three parts: 1. General information, 2. Health literacy (including knowledge, understanding, and other sub-aspects), and 3. Protective behaviors against chemical exposure. Each part of the questionnaire had a reliability index of 0.60 or higher. The reliability of the 2nd and 3rd parts of the questionnaire were as follows: sub-sections of part 2 had a Kuder-Richardson (KR-20) coefficient of 0.79 and Cronbach’s alpha (α) coefficient of 0.85-0.86, while part 3 had an α of 0.88. Risk of chemical exposure was assessed using a Cholinesterase Reactive Paper test administered by a finger-prick blood test. Data was analyzed using the Spearman correlation and binary logistic regression. The study was reviewed by the Human Research Ethics Committee with the approval date: August 9, 2021, and expiry date: August 9, 2022. Results Most participants had moderate levels of overall HL (48.8%) and PPB (44.6%). There was a statistically significant positive correlation between HL and PPB (rs(478) = 0.70, p<.005). Logistic regression analysis demonstrated that HL had a statistically significant positive association with PPB (p<.001, OR = 6.57, 95% CI 3.95, 10.94) and was associated with blood cholinesterase levels. Conclusions These findings highlight the need for increased health literacy among farmers in Thailand to ensure correct protective behaviors against chemical exposure and reduce the adverse effects of pesticide exposure on human health.
Structural Estimation of Markov Decision Processes in High-Dimensional State Space with Finite-Time Guarantees
Authors: Zeng Siliang , Hong Mingyi , Garcia Alfredo
Published: September 2024

Researchers have introduced a new algorithm to estimate structural models of dynamic decisions by human agents, addressing the challenge of high computational complexity. Traditionally, this task involves a nested structure: an inner problem identifying an optimal policy and an outer problem maximizing a measure of fit. Previous methods have struggled with large discrete state spaces or high-dimensional continuous state spaces, often sacrificing reward estimation accuracy. The new approach combines policy improvement with a stochastic gradient step for likelihood maximization, ensuring accurate reward estimation without compromising computational efficiency. This single-loop algorithm, designed to handle high-dimensional state spaces, converges to a stationary solution with finite-time guarantees. When the reward is linearly parameterized, it approximates the maximum likelihood estimator sublinearly, offering a robust solution for complex decision modeling tasks.
Managing naïve multiple sclerosis patients: how firstline oral medications modify educational time
Authors: Sartori Arianna , Pasquin Fulvio , Griggio Stefania , Dinoto Alessandro , Baldini Sara , Bratina Alessio , Bosco Antonio , Manganotti Paolo
Published: September 2024

Multiple sclerosis is a chronic disease requiring a multidisciplinary approach. Multiple sclerosis nurses are involved in all aspects of care, in particular in patients' education about disease-modifying drugs. The availability of oral firstline treatments has had a considerable impact on disease management. The aim of this study was to valuate if the introduction of oral therapies has led to a change in nurses' time spent on education, empowerment and training. A retrospective study was conducted enrolling naïve patients with relapsing-remitting mutliple sclerosis. Working time spent by nurses was compared between patients treated with oral versus injectable drugs. Correlations between time and clinical variables were investigated. A total of 55 patients were enrolled (34 using injectable and 21 using oral medication). For the oral group, less work time (P=0.018) and number of meetings (P=0.004) were needed. Dimethyl fumarate needed a lower number of meetings compared with other drugs. The availability of oral drugs seemed to reduce the amount of working time nurses spent with naïve patients' discussing education and treatment.
Living with multiple sclerosis: the South Asian experience
Authors: Bharadia Trishna
Published: September 2024

Multiple sclerosis (MS) is a chronic neurological condition that affects more than 150 000 people in the UK, but there is relatively little known about the experiences of people with South Asian heritage who are affected by the condition. In this article, the author explores how being of South Asian heritage has shaped her experience of living with MS and what MS nurses can do to better support people like her.
Key takeaway messages from the MS Trust conference 2024
Authors: Naik Paru
Published: September 2024

Health Professionals come together every year at the MS Trust Conference to share insights and further their knowledge in the different aspects of caring for people living with MS. A key element is to share the various tools available and hear from the experts. This article presents the key themes from just some of the topical subjects discussed during the MS Trust Conference this year.
Turn Compensation Control Development and Analysis for a Self-Propelled Sprayer Chassis Suspension System
Authors: Huerta-Musil Joel , Adams Bailey
Published: September 2024

Highlights

An Experimental sprayer chassis suspension control system was developed and evaluated in headland turns.

Turning evaluation performance metrics and methods were conceptualized in the context of sprayers.

The Experimental chassis suspension system showed stability and comfort increases during aggressive turns.

Boom stability improved significantly after completion of the turn for the Experimental suspension system.

Abstract.A challenging economic, environmental, and regulatory landscape causes the need for efficient agricultural machinery. The performance of self-propelled sprayers depends on their ability to deposit chemicals accurately and efficiently, and increased machine sizes and faster driving speeds require consideration for sprayer chassis stability. One method of improving this stability is using variable damping elements in the sprayer chassis suspension system. In this work, an Experimental sprayer chassis suspension system that implemented turning event detection and variable damping control was developed for headland turning events. The Experimental chassis suspension system was tested for a constant speed headland turn maneuver at 10 to 25 m turn radii. The performance of the Experimental system was quantified in terms of operator comfort and operator health, chassis roll and roll rate amplitudes, and boom height sensor standard deviation, and this performance was compared to a Baseline sprayer suspension configuration. From the data collected, the Experimental suspension system improved chassis roll and roll rate stability by 30% to 40% for the entry portion of the turning event regardless of turn radius while also showing a 5% increase in ride quality. The need for tuning the damping level to the chassis yaw rate was identified from decreased comfort performance metrics at larger turn radii. Boom height stability improved significantly for Experimental suspension configurations, particularly after the turning event, showing an 8% to 21% improvement in boom height standard deviation. Further exploration of control parameters and their effects outside turning events should be conducted to ensure optimal control law settings based on machine configurations. Keywords: Chassis suspension, Control, Performance, Self-propelled sprayer, Stability, Turn event, Variable damping.
The Inconvenience Drive of the Comedic
Authors: Zupančič Alenka
Published: September 2024

Abstract: The article proposes a reading of Berlant's On the Inconvenience of Other People that focuses on their understanding of the comedic and the way the latter intersects with the book's other major themes, sexuality and politics. It shows how Berlant's project could be seen as a conceptual proposal, an invitation to build with what keeps us apart. The comedic - which Berlant distinguishes from comedy as a genre form - is a double movement, both of loosening an object, making it available for different kinds of attachment, and of proceeding, persisting in this difference and effectively making other, different connections. Particular attention is paid to the interesting connection between the notion of the inconvenience and that of desire and drive. The author also discusses some differences between Berlant's and her understanding of comedy.
Holistic and in situ calibration method for a spectral-temporally modulated Mueller spectropolarimeter
Authors: Zhao Zhe , Wu Jinxian , Zhong Hui , Ma Xiang , Li Yanqiu
Published: September 2024

The spectral-temporally modulated Mueller spectropolarimeter (STMSP) offers advantages of broader band limitation, better resolution, and faster detection speed. However, the current STMSP calibration method separates the polarization state generator and analyzer, necessitating subsequent recombination, which is inefficient and unstable. In this paper, a holistic and in situ calibration method for STMSP is proposed. It only requires insertion of a polarizer as a reference sample, eliminating the need for separate calibration and recombination. The STMSP is calibrated in situ as a whole, addressing the misalignment error of the spectral modulation module, the total polarimetric errors of the temporal modulation module, and the spectral modulation transfer function of the spectrometer. Experimental results demonstrate high accuracy, with a root mean square error (RMSE) of 0.0004, which is an order of magnitude lower than that of the dual-rotating retarder spectropolarimeter (DRRSP) after eigenvalue calibration. This demonstrates its potential for enabling faster and more accurate acquisition of the Mueller spectra.