bluuebunny/crossref_metadata_2025 huggingface dataset:
Imaging Brain Injury in Former National Football League Players
Authors: Rubin Leah H. , Du Yong , Sweeney Shannon Eileen , O’Toole Riley , Thomas Cykyra L. , Zandi Adeline G. , Shinehouse Laura K. , Brosnan Mary Katherine , Nam Hwanhee , Burke Michael E. , Bureau Samantha C. , Kilgore Jessica J. , Yoon Mark , Soule Ana R. , Lesniak Wojciech G. , Minn Il , Rowe Steven P. , Holt Daniel P. , Hall Andrew W. , Mathews William B. , Smith Gwenn S. , Nowinski Christopher J. , Kassiou Michael , Dannals Robert F. , Pomper Martin G. , Coughlin Jennifer M.
Published: October 2023

Importance

Pilot studies that involved early imaging of the 18 kDa translocator protein (TSPO) using positron emission tomography (PET) indicated high levels of TSPO in the brains of active or former National Football League (NFL) players. If validated further in larger studies, those findings may have implications for athletes involved in collision sport.

Objective

To test for higher TSPO that marks brain injury and repair in a relatively large, unique cohort of former NFL players compared with former elite, noncollision sport athletes.

Design, Setting, and Participants

This cross-sectional study used carbon 11–labeled N,N-diethyl-2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide positron emission tomography ([11C]DPA-713 PET) data from former NFL players within 12 years of last participation in the NFL and elite noncollision sport athletes from across the US. Participants were enrolled between April 2018 and February 2023.

Main outcomes and measures

Regional [11C]DPA-713 total distribution volume from [11C]DPA-713 PET that is a measure of regional brain TSPO; regional brain volumes on magnetic resonance imaging; neuropsychological performance, including attention, executive function, and memory domains.

Results

This study included 27 former NFL players and 27 former elite, noncollision sport athletes. Regional TSPO levels were higher in former NFL players compared with former elite, noncollision sport athletes (unstandardized β coefficient, 1.08; SE, 0.22; 95% CI, 0.65 to 1.52; P < .001). The magnitude of the group difference depended on region, with largest group differences in TSPO in cingulate and frontal cortices as well as hippocampus. Compared with noncollision sport athletes, former NFL players performed worse in learning (mean difference [MD], −0.70; 95% CI, −1.14 to −0.25; P = .003) and memory (MD, −0.77; 95% CI, −1.24 to −0.30; P = .002), with no correlation between total gray matter TSPO and these cognitive domains.

Conclusions and relevance

In this cross-sectional study using [11C]DPA-713 PET, higher brain TSPO was found in former NFL players compared with noncollision sport athletes. This finding is consistent with neuroimmune activation even after cessation of NFL play. Future longitudinal [11C]DPA-713 PET and neuropsychological testing promises to inform whether neuroimmune-modulating therapy may be warranted.
Association Between Slow-Wave Sleep Loss and Incident Dementia
Authors: Himali Jayandra J. , Baril Andree-Ann , Cavuoto Marina G. , Yiallourou Stephanie , Wiedner Crystal D. , Himali Dibya , DeCarli Charles , Redline Susan , Beiser Alexa S. , Seshadri Sudha , Pase Matthew P.
Published: October 2023

Importance

Slow-wave sleep (SWS) supports the aging brain in many ways, including facilitating the glymphatic clearance of proteins that aggregate in Alzheimer disease. However, the role of SWS in the development of dementia remains equivocal.

Objective

To determine whether SWS loss with aging is associated with the risk of incident dementia and examine whether Alzheimer disease genetic risk or hippocampal volumes suggestive of early neurodegeneration were associated with SWS loss.

Design, Setting, and Participants

This prospective cohort study included participants in the Framingham Heart Study who completed 2 overnight polysomnography (PSG) studies in the time periods 1995 to 1998 and 2001 to 2003. Additional criteria for individuals in this study sample were an age of 60 years or older and no dementia at the time of the second overnight PSG. Data analysis was performed from January 2020 to August 2023.

Exposure

Changes in SWS percentage measured across repeated overnight sleep studies over a mean of 5.2 years apart (range, 4.8-7.1 years).

Main Outcome

Risk of incident all-cause dementia adjudicated over 17 years of follow-up from the second PSG.

Results

From the 868 Framingham Heart Study participants who returned for a second PSG, this cohort included 346 participants with a mean age of 69 years (range, 60-87 years); 179 (52%) were female. Aging was associated with SWS loss across repeated overnight sleep studies (mean [SD] change, −0.6 [1.5%] per year; P < .001). Over the next 17 years of follow-up, there were 52 cases of incident dementia. In Cox regression models adjusted for age, sex, cohort, positivity for at least 1 APOE ε4 allele, smoking status, sleeping medication use, antidepressant use, and anxiolytic use, each percentage decrease in SWS per year was associated with a 27% increase in the risk of dementia (hazard ratio, 1.27; 95% CI, 1.06-1.54; P = .01). SWS loss with aging was accelerated in the presence of Alzheimer disease genetic risk (ie, APOE ε4 allele) but not hippocampal volumes measured proximal to the first PSG.

Conclusions and Relevance

This cohort study found that slow-wave sleep percentage declined with aging and Alzheimer disease genetic risk, with greater reductions associated with the risk of incident dementia. These findings suggest that SWS loss may be a modifiable dementia risk factor.
Maternal and Infant Antibiotic and Acid Suppressant Use and Risk of Eosinophilic Esophagitis
Authors: Jensen Elizabeth T. , Svane Helene M. , Erichsen Rune , Kurt Gencer , Heide-Jorgensen Uffe , Sorensen Henrik T. , Dellon Evan S.
Published: October 2023

Importance

Eosinophilic esophagitis (EoE), a chronic disease with significant patient and health care burden, has increased rapidly in incidence across many countries. Elucidating risk factors for disease development is a priority for health care practitioners and patients.

Objective

To evaluate the association of maternal and infant use of antibiotics and acid suppressants with the development of EoE.

Design, Setting, and Participants

This was a population-based, case-control study of pediatric EoE (1996-2019) in Denmark using pathology, prescription, birth, inpatient, and outpatient health registry data and with complete ascertainment of all EoE cases among Danish residents born between 1997 and 2018. Study data were analyzed from September 2020 to August 2023.

Exposures

Maternal and infant use of antibiotics and acid suppressants, examining medication class, timing, and frequency of use.

Main Outcome and Measure

Development of EoE.

Results

Included in the study was a total of 392 cases and 3637 sex- and year of birth–matched controls with a median (IQR) age of 11.0 (6.0-15.0) years, 2772 male individuals (68.8%), and 1257 female individuals (31.2%). Compared with children with no antibiotic prescriptions filled during infancy, those with any use of an antibiotic had an associated 40% increase in risk of EoE (adjusted odds ratio [aOR], 1.4; 95% CI, 1.1-1.7). Those with 3 or more prescriptions had an associated 80% increase in risk of EoE (aOR, 1.8; 95% CI, 1.3-2.5). Frequency of maternal antibiotic use was associated with an increased risk (1 prescription: aOR, 1.4; 95% CI, 1.0-1.8; 3≤ prescriptions: aOR, 2.1; 95% CI, 1.4-3.2). Risk was highest for use in the third trimester and in the first 6 months from birth. Any acid suppressant use in infancy was associated with increased risk of EoE (aOR, 15.9; 95% CI, 9.1-27.7). Restriction of cases to those diagnosed at 5 years or older yielded similar results (aOR, 11.6; 95% CI, 5.5-24.8). For maternal use, 3 or more prescriptions were associated with an increased risk of EoE for her offspring (aOR, 5.1; 95% CI, 1.8-14.8).

Conclusions and Relevance

Maternal and infant antibiotic use were associated with increased risk of developing EoE, in a dose-response manner, and the magnitude of association was highest for exposure near the time of delivery. Increased risk was also observed with maternal and infant acid suppressant use. Exposure during early life, a period of known developmental susceptibility, may confer the greatest risk and opportunity for risk mitigation.
What Parents Should Know About Gun Safety in the Home and Vehicle
Authors: Palmer Rebecca J. , DeWitt Leila H. , Thompson Lindsay A.
Published: October 2023

This Patient Page describes safety measures parents can take to protect children from gun violence.
Th17 cells target the metabolic miR‐142‐5p–succinate dehydrogenase subunit C/D (SDHC/SDHD) axis, promoting invasiveness and progression of cervical cancers
Authors: Pohlers Maike , Gies Selina , Taenzer Tanja , Stroeder Russalina , Theobald Laura , Ludwig Nicole , Kim Yoo‐Jin , Bohle Rainer Maria , Solomayer Erich Franz , Meese Eckart , Hart Martin , Walch‐Rückheim Barbara
Published: October 2023

During cervical carcinogenesis, T‐helper (Th)‐17 cells accumulate in the peripheral blood and tumor tissues of cancer patients. We previously demonstrated that Th17 cells are associated with therapy resistance as well as cervical cancer metastases and relapse; however, the underlying Th17‐driven mechanisms are not fully understood. Here, using microarrays, we found that Th17 cells induced an epithelial‐to‐mesenchymal transition (EMT) phenotype of cervical cancer cells and promoted migration and invasion of 2D cultures and 3D spheroids via induction of microRNA miR‐142‐5p. As the responsible mechanism, we identified the subunits C and D of the succinate dehydrogenase (SDH) complex as new targets of miR‐142‐5p and provided evidence that Th17–miR‐142‐5p‐dependent reduced expression of SDHC and SDHD mediated enhanced migration and invasion of cancer cells using small interfering RNAs (siRNAs) for SDHC and SDHD, and miR‐142‐5p inhibitors. Consistently, patients exhibited high levels of succinate in their serum associated with lymph node metastases and diminished expression of SDHD in patient biopsies correlated with increased numbers of Th17 cells. Correspondingly, a combination of weak or negative SDHD expression and a ratio of Th17/CD4+ T cells > 43.90% in situ was associated with reduced recurrence‐free survival. In summary, we unraveled a previously unknown molecular mechanism by which Th17 cells promote cervical cancer progression and suggest evaluation of Th17 cells as a potential target for immunotherapy in cervical cancer.
Effect of Heat Treatment on Interface Behavior and Fatigue Property of 316L/2Cr13 Multilayered Steel
Authors: Zhou Xin , Cao Rui , Ma Jingping , Jiang Xiaoxia , Yan Yingjie
Published: October 2023

In this study, multilayered stainless steel (MLS) composed of the austenitic stainless steel 316 L and the martensitic stainless steel 2Cr13 is prepared by the cumulative rolling method. Specifically, changes in interface and fatigue properties before and after the heat treatment are verified by scanning electron microscope, tensile test, and fatigue test. In the results, it is revealed that common grains appear at the interface after the heat treatment. Although the overall mechanical properties are improved, the interfacial bonding strength is increased and the plasticity is greatly improved after heat treatment, the fatigue properties are greatly decreased simultaneously. The main cause is that during the rolling process, large deformation leads to grain fragmentation as well as the generation of a large number of subgrains, resulting in higher dislocation density and increased deformation resistance. Therefore, the fatigue performance of MLS in as‐rolled state is better than that of MLS in the heat‐treatment state. In addition, fatigue fracture analysis indicates that cracks usually initiate at the 2Cr13 layer or at the interface between the 316 L layer and the 2Cr13 layer. Ultimately, in this study, the quadratic relationship between tensile strength and fatigue limit is analyzed through fatigue ratio to predict fatigue limit.
Pd/Cu Co‐Catalyzed ortho‐Arylation of Aryl Iodides via Radical Intermediates with Aryl Diazonium Salts
Authors: Fu Ying , Guo Liang‐Liang , Chen Xi , Chen Hao , Liu Jia‐Jia , Li Fang‐Rong , Xiao Cai‐Qin , Du Zhengyin
Published: October 2023

A Cu/Pd co‐catalyzed Catellani‐type ortho arylation reaction of iodoarenes with aryl diazonium salts has been developed. Aryl radicals that derived from aryl diazonium salts were regioselectively installed at ortho position of iodoarenes via palladium catalyzed C−H activation. Mechanistic studies showed that, in contrast to classical Pd0−PdII−PdIV−PdII−Pd0 catalytic cycle, this radical cascades performed via a Pd0−PdII−PdIII−PdI−Pd0 cycle.
Fam20C Kinase as a Key Regulator of Bevacizumab Resistance in Mesenchymal Glioblastoma
Authors: Kim Chan Il , Kim Sooheon , Park Seong‐Min , Kim Sung Soo , Kwon Hyung Joon , Lin Weiwei , Park Saewhan , Ha Seokjun , Ha Kyung Hee , Park Sanha , Park Seung Min , Kim Tae Hoon , Kim Kyung‐Hee , Kim Yun‐Hee , Kim Jong Heon , Park Jong Bae
Published: October 2023

A significant hurdle in treating glioblastoma (GBM) is addressing the development of drug resistance. In this study, the role of Family of Sequence Similarity 20, Member C (Fam20C) as a central player in bevacizumab resistant GBM mouse model is investigated. In vivo analyses confirm that Fam20C upregulation accelerates drug resistance and correlates with tumor progression. Proteomic analyses of conditioned media and cell lysates subsequent to Fam20C knockout (KO) in GBM cells reveal the regulatory role of Fam20C in both intracellular and extracellular aspects of epithelial‐mesenchymal transition (EMT) and genes associated with AKT signaling. Moreover, In vitro experiments demonstrate that Fam20C activates the AKT signaling pathway, promoting cell proliferation. Elevated levels of Fam20C are observed in human GBM, particularly in the mesenchymal subtype, which correlates with diminished survival rates and increased resistance to various drugs, including temozolomide (TMZ), bevacizumab, epidermal growth factor receptor (EGFR) inhibitors, and other antibody‐based drugs. Notably, even in cases of resistance to gefitinib and hepatocyte growth factor (HGF) antibodies, Fam20C expression is elevated. These findings highlight the pivotal role of Fam20C in driving drug resistance in GBM, suggesting it as a promising target for combination therapies aimed at surmounting this formidable resistance barrier.
I2/PPh3‐Mediated Cyclization of Enaminones with Sodium Sulfinates: A Protocol for the Synthesis of 3‐Thiolated Chromones
Authors: Du Jing , Zhao Shi‐Yi , Hu Zhi‐Chao , Dong Zhi‐Bing
Published: October 2023

An I2/PPh3‐mediated synthesis of 3‐thiolated chromones starting from 2‐hydroxyphenylenones and sodium sulfinates was reported. This method features one pot manner, metal‐free, easy performance, readily available starting materials and illustrating potential value for some biologically or pharmaceutically active compounds. In addition, a possible mechanism was proposed based on the control experiments.
Glycan Metabolic Fluorine Labeling for In Vivo Visualization of Tumor Cells and In Situ Assessment of Glycosylation Variations
Authors: Chen Dongxia , Lin Yaying , Fan Yifan , Li Lingxuan , Tan Chenlei , Wang Junjie , Lin Hongyu , Gao Jinhao
Published: October 2023

The abnormality in the glycosylation of surface proteins is critical for the growth and metastasis of tumors and their capacity for immunosuppression and drug resistance. This anomaly offers an entry point for real‐time analysis on glycosylation fluctuations. In this study, we report a strategy, glycan metabolic fluorine labeling (MEFLA), for selectively tagging glycans of tumor cells. As a proof of concept, we synthesized two fluorinated unnatural monosaccharides with distinctive 19F chemical shifts (Ac4ManNTfe and Ac4GalNTfa). These two probes could undergo selective uptake by tumor cells and subsequent incorporation into surface glycans. This approach enables efficient and specific 19F labeling of tumor cells, which permits in vivo tracking of tumor cells and in situ assessment of glycosylation changes by 19F MRI. The efficiency and specificity of our probes for labeling tumor cells were verified in vitro with A549 cells. The feasibility of our method was further validated with in vivo experiments on A549 tumor‐bearing mice. Moreover, the capacity of our approach for assessing glycosylation changes of tumor cells was illustrated both in vitro and in vivo. Our studies provide a promising means for visualizing tumor cells in vivo and assessing their glycosylation variations in situ through targeted multiplexed 19F MRI.
Gel based on modified chitosan for oil spill cleanup
Authors: Yudaev Pavel , Semenova Anastasia , Chistyakov Evgeniy
Published: October 2023

A method has been developed for obtaining a polymer porous gel and coating based on nontoxic and environmentally friendly components: chitosan, citral, and glutaraldehyde. The chemical structure and morphology of the polymer gel were investigated by infrared spectroscopy and scanning electron microscopy, respectively. The contact angles were determined using a goniometer, and the water and oil absorption of the gel were determined by the gravimetric method based on changes in the gel mass. Measurement of the contact angle θ of transmission oil and water drops on the coating surface showed the hydrophobic nature of the coating (θ = 90° for water and θ = 0° for oil). Study of the sorption properties of the resulting gel showed high sorption capacity with respect to transmission oil (9.05 kg/kg) and low sorption capacity with respect to water (2.46 kg/kg). It was found that after oil desorption from the loaded aerogel, it can be reused. The potential possibility of recycling the spent gel through its biodegradation in the soil was shown. Because of the excellent sorption capacity, high porosity, low density, and soil degradability, the developed gel has a great potential for application in the field of environmental purification from oil pollution.
Ageing abandoned, lost, and discarded lobster fishing gear based on fouling assemblages
Authors: Legare Bryan J. , Nichols Owen C. , Ludwig Laura R.
Published: October 2023

Abandoned, lost, or otherwise discarded fishing gear (ALDFG) is a by‐product of many fisheries. ALDFG impacts extend beyond the targeted species and include by‐catch, habitat degradation, and increased plastic in the environment. In particular ALDFG such as lobster gear attracts a succession of fouling organisms, increasing species diversity and productivity.

In Cape Cod Bay, Massachusetts, USA, a seasonal lobster gear closure occurs for the protection of North Atlantic right whales (Eubalaena glacialis), allowing for the removal of ALDFG. In this study, the percentage cover of fouling organisms on recovered gear was used to model the age of the recovered gear (of indeterminate age because of missing tags).

Between 2017 and 2021, a total of 379 traps were photo documented, of which 223 were of known age (1–22 years) and 156 were of unknown age. The age of the unknown traps was modelled utilizing a random forest algorithm using traps with a known age as a training library.

High correlations between modelled ages and known ages (R2 = 0.634, P < 0.001*) slightly underestimated the age of the traps by 1.2–1.8 years, but are sufficient for developing an age distribution. The majority (79%) of traps were recovered off Provincetown and averaged 10–11 years old. Approximately 50% of the traps recovered in Cape Cod Bay were deposited or lost between 2005 and 2010.

Calculating the age of ALDFG aids in determining the loss rate of gear and in identifying high concentrations of untended gear that can be recycled or reused. This analysis allows practitioners to understand the scale of the problem, helps quantify the quantity of gear in the ocean, and helps identify the areas most affected. This information improves the effectiveness of removal efforts by focusing on discrete areas of recurring and recent gear loss.
Fiber chromatographic enabled process intensification increases monoclonal antibody product yield
Authors: Anderson Sean M. , Seto Elbert , Chau David , Lee Brian , Vail Andrew , Ding Sheng , Voloshin Alexei , Nagel Mark
Published: October 2023

The most straightforward method to increase monoclonal antibody (mAb) product yield is to complete the purification process in less steps. Here, three different fiber chromatographic devices were implemented using a holistic approach to intensify the mAb purification process and increase yield. Fiber protein A (proA) chromatography was first investigated, but traditional depth filtration was not sufficient in reducing the contaminant load as the fiber proA device prematurely fouled. Further experimentation revealed that chromatin aggregates were the most likely reason for the fiber fouling. To reduce levels of chromatin aggregates, a chromatographic clarification device (CCD) was incorporated into the process, resulting in single‐stage clarification of harvested cell culture fluid and reduction of DNA levels. The CCD clarified pool was then successfully processed through the fiber proA device, fully realizing the productivity gains that the fiber technology offers. After the proA and viral inactivation neutralization (VIN) hold step, the purification process was further intensified using a novel single‐use fiber‐based polishing anion exchange (AEX) material that is capable of binding both soluble and insoluble contaminants. The three‐stage fiber chromatographic purification process was compared to a legacy five‐step process of dual‐stage depth filtration, bead‐based proA chromatography, post‐VIN depth filtration, and bead‐based AEX chromatography. The overall yield from the five‐step process was 60%, while the fiber chromatographic‐enabled intensified process had an overall yield of 70%. The impurity clearance of DNA and host cell protein (HCP) for both processes were within the regulatory specification (<100 ppm HCP, <1 ppb DNA). For the harvest of a 2000 L cell culture, the intensified process is expected to increase productivity by 2.5‐fold at clarification, 50‐fold at the proA step, and 1.6‐fold in polishing. Relative to the legacy process, the intensified process would reduce buffer use by 1088 L and decrease overall process product mass intensity by 12.6%.
Interpreting stakeholder ecosystems through relational stakeholder theory: The case of a highly contested megaproject
Authors: Corazza Laura , Cottafava Dario , Torchia Daniel , Dhir Amandeep
Published: October 2023

Managing stakeholders' concerns in megaprojects with an inclusive and ethical vision is a current open challenge. To overcome company‐centered stakeholder‐management practices, an ecosystem view, (i.e., one based on the network of relationships among involved stakeholders), should be adopted by designing bottom‐up participatory stakeholder mapping processes that include the stakeholders affected by the construction of a megaproject. This paper presents an analysis of the stakeholder ecosystem of a contested megaproject in Italy (the Turin–Lyon high‐speed rail) aimed at identifying similarities and discrepancies in stakeholder identification and prioritization between the managers' perception and an ecosystem point of view. The study followed a mixed‐method approach. By coding the self‐declared statements from 21 interviews with middle and top managers of the organization in charge of the construction and visualizing the emerging network of actors through a social network analysis and the use of centrality degrees, the most relevant stakeholders are identified. Our findings reveal how the prioritization of stakeholders obtained through the centrality degrees significantly differs from what the managers declare in reference to the concept of salience, highlighting how a bottom‐up stakeholder mapping process—by including the stakeholders themselves in the mapping process—should be designed and reiterated during the whole life of a megaproject in order to adopt an inclusive stakeholder management approach.
Concordance between patient‐reported and physician‐documented comorbidities and symptoms among Stage 4 breast cancer patients
Authors: Umashankar Saumya , Basu Amrita , Esserman Laura , van't Veer Laura , Melisko Michelle E.
Published: October 2023

Background

Comorbidities and symptoms in metastatic breast cancer patients impact treatment decisions and influence prognosis and quality of life. The objective of this study is to examine the concordance between physician documentation and patient reports of comorbidities and symptoms to understand their comparative effectiveness.

Methods

New patients with metastatic breast cancer completed an electronic intake survey assessing patient health history and symptoms. Physician documentation across 54 comorbidities and 42 symptoms was abstracted from notes for the corresponding clinic visits between November 2016 and March 2020. Concordance between patient reports and medical records for each condition and hazards ratios for each patient versus physician reported comorbidity and symptom were assessed.

Results

A total of 168 patients were included in the analysis (age, median = 56 years, range = 29–86 years; 131 white [78.9%]). Twenty‐three of 54 comorbidities had a moderate to high level of agreement between patients and physicians (κ ≥ 0.40). Physicians documented higher numbers of comorbidities that can be objectively measured which also had higher concordance (e.g., diabetes [κ = 0.83] and hypertension [κ = 0.79]) while patients reported higher numbers of comorbidities that are more subjective which also had lower concordance (anxiety [κ = 0.30], GERD [κ = 0.36]). One physician‐documented and two patient‐reported comorbidities were significantly associated with survival (p < 0.05). Only 2 of 42 symptoms had a moderate to high level of agreement between patients and physicians. One physician‐documented and nine patient‐reported symptoms were significantly associated with decreased survival (p < 0.05).

Conclusion

Agreement between patients' and physicians' reporting of comorbidities varies substantially, and patient reports can complement physician documentation. Physicians significantly underreported symptoms versus patients; thus, concordance was also low. Multiple patient‐reported symptoms were predictive of survival; thus, incorporating them can provide more informative estimates of predicted survival.
The effectiveness of ablative and non‐surgical therapies for early hepatocellular carcinoma: Systematic review and network meta‐analysis of randomised controlled trials
Authors: South Emily , Wade Ros , Anwer Sumayya , Sharif‐Hurst Sahar , Harden Melissa , Fulbright Helen , Dias Sofia , Simmonds Mark , Rowe Ian , Thornton Patricia , Wah Tze Min , Eastwood Alison
Published: October 2023

Background & Aims

Non‐surgical therapies are frequently used for patients with early or very early hepatocellular carcinoma (HCC). The aim of this systematic review and network meta‐analysis (NMA) was to evaluate and compare the effectiveness of ablative and non‐surgical therapies for patients with small HCC.

Methods

Nine databases were searched (March 2021) along with clinical trial registries. Randomised controlled trials (RCTs) of any ablative or non‐surgical therapy versus any comparator in patients with HCC ≤3 cm were eligible. Risk of bias (RoB) was assessed using the Cochrane RoB 2 tool. The effectiveness of therapies was compared using NMA. Threshold analysis was undertaken to identify which NMA results had less robust evidence.

Results

Thirty‐seven eligible RCTs were included (including over 3700 patients). Most were from China (n = 17) or Japan (n = 7). Sample sizes ranged from 30 to 308 patients. The majority had a high RoB or some RoB concerns. No RCTs were identified for some therapies and no RCTs reported quality of life outcomes. The results of the NMA and treatment effectiveness rankings were very uncertain. However, the evidence demonstrated that percutaneous ethanol injection was worse than radiofrequency ablation for overall survival (hazard ratio [HR]: 1.45, 95% credible interval [CrI]: 1.16–1.82), progression‐free survival (HR: 1.36, 95% CrI: 1.11–1.67), overall recurrence (relative risk [RR]: 1.19, 95% CrI: 1.02–1.39) and local recurrence (RR: 1.80, 95% CrI: 1.19–2.71). The threshold analysis suggested that robust evidence was lacking for some comparisons.

Conclusions

It is unclear which treatment is most effective for patients with small HCC because of limitations in the evidence base. It is also not known how these treatments would impact on quality of life. Further high quality RCTs are needed to provide robust evidence but may be difficult to undertake.
Early skeletal muscle loss in adolescent and young adult cancer patients treated with anthracycline chemotherapy
Authors: Wooten Savannah V. , Wang Fei , Roth Michael E. , Liu Guanshu , Livingston J. Andrew , Amini Behrang , Gilchrist Susan C. , Hildebrandt Michelle , Kleinerman Eugenie S.
Published: October 2023

Background

Early skeletal muscle loss has been observed in adolescent and young adult (AYA) sarcoma patients undergoing treatment. Identification of individuals within the AYA populace that are at greatest risk of anthracycline‐induced skeletal muscle loss is unknown. Moreover, investigations which seek out underlying causes of skeletal muscle degradation during chemotherapy are critical for understanding, preventing, and reducing chronic health conditions associated with poor skeletal muscle status.

Methods

Computed tomography (CT) scans were used to investigate changes in skeletal muscle of 153 AYA sarcoma and Hodgkin lymphoma patients at thoracic vertebra 4 after anthracycline treatment. Images were examined at three time points during the first year of treatment. In parallel, we used translational juvenile mouse models to assess the impact of doxorubicin (DOX) in the soleus and gastrocnemius on muscle wasting.

Results

Significant reductions in total skeletal muscle index and density were seen after chemotherapy in AYA cancer patients (p < 0.01 & p = 0.04, respectively). The severity of skeletal muscle loss varied by subgroup (i.e., cancer type, sex, and treatment). Murine models demonstrated a reduction in skeletal muscle fiber cross‐sectional area, increased apoptosis and collagen volume for both the soleus and gastrocnemius after DOX treatment (all p < 0.05). After DOX, hindlimb skeletal muscle blood flow was significantly reduced (p < 0.01).

Conclusion

Significant skeletal muscle loss is experienced early during treatment in AYA cancer patients. Reductions in skeletal muscle blood flow may be a key contributing factor to anthracycline doxorubicin induced skeletal muscle loss.
The impact of the COVID‐19 pandemic on radiotherapy delivery in Japan: An observational study based on the national database
Authors: Tamari Keisuke , Kishigami Maiko , Nagata Yasushi , Mizowaki Takashi , Kodaira Takeshi , Onishi Hiroshi , Ogawa Kazuhiko , Shioyama Yoshiyuki , Shigematsu Naoyuki , Uno Takashi
Published: October 2023

Background

This study analyzed the impact of the coronavirus disease 2019 (COVID‐19) pandemic on radiotherapy delivery in Japan using a high‐quality Japanese national database based on universal health coverage.

Methods

We performed a retrospective observational study using National Database of Health Insurance Claims and Specific Health Checkups of Japan open data focused on radiotherapy between fiscal year (FY) 2019 and FY2020 and the number of COVID‐19 cases from the Ministry of Health, Labour, and Welfare. We statistically analyzed the relationship between the number of COVID‐19 cases and the number of radiotherapy deliveries in Japan as a whole and by prefecture.

Results

The total number of external beam radiotherapy (EBRT) fractions was 4,472,140 in FY2019 and 4,227,673 in FY2020 (−5.8%). EBRT courses were 250,395 in FY2019 and 240,329 in FY2020 (−4.0%), stereotactic radiotherapy courses were 27,619 in FY2019 and 31,786 in FY2020 (+15.1%), and single‐fraction palliative radiotherapy courses were 4124 in FY2019 and 5255 in FY2020 (+21.5%). The total number of breast and prostate hypofractionated radiotherapy (HFRT) fractions was 155,773 and 48,188 in FY2019, and 200,256 and 84,230 in FY2020 (+28.6% and +74.8%), respectively. In the Pearson correlation analysis, EBRT fractions were lower, and breast HFRT fractions were higher in prefectures with more COVID‐19 cases.

Conclusions

Overall, radiotherapy delivery in Japan was relatively stable after the pandemic, with an increase in HFRT. Also, EBRT fractions decreased, and breast HFRT were more likely to be used in prefectures with more COVID‐19 cases.
‘I guess the ending is the price you pay’. Working at relational depth in a seven‐session model: The impact of regular planned endings on counsellors
Authors: Chambers Liz , Pendle Andy
Published: October 2023

Background

Evidence suggests that the quality of the therapeutic relationship impacts the outcome of therapy, with the ending phase having the potential to elicit painful and difficult emotions. There is limited research on this phase of the therapeutic relationship.

Aims

The study aimed to explore the lived experiences of counsellors when ending with clients in short‐term planned settings those relationships in which they have worked at relational depth.

Method

Interpretative phenomenological analysis was used to evaluate the counsellors' lived experiences of ending therapeutic relationships. Online semi‐structured interviews took place with six trainee and qualified counsellors who volunteered as counsellors for a local charity.

Findings

Three main themes were identified during the study—impact of ending, impact of short‐term work and professional issues. Findings indicated that working at relational depth in short‐term counselling could elicit unprocessed powerful emotions within the ending phase of therapy.

Limitations

A small sample size limits the wider application of these findings.

Implications

Further guidance and support are needed for trainee and qualified practitioners in the management and experience of ending counselling relationships within short‐term work, including the exploration of counsellors' self‐disclosure. Implications for practice include the need for supervisors and counsellors to be proactive in managing reflective practice within supervision, supervisors recognising and challenging supervisees' non‐disclosure and counsellors looking at further ways for self‐reflection on endings in counselling relationships.

Conclusion

The ending phase for counsellors working at relational depth within a seven‐session model can elicit powerful emotions, positive experiences and challenges.
Looking for negativity! How review sentiment and review subjectivity form review helpfulness across cultures
Authors: Shah Aakash , Gohary Ali , Lie David
Published: October 2023

Nowadays, many consumers rely heavily on product reviews before making decisions; however, not all reviews are similar in terms of sentiment and helpfulness. Moreover, reviewers' linguistic styles vary according to their culture. Although various multinational companies such as eBay and Amazon operate worldwide, little research has been devoted to understanding how review sentiment influences the subjectivity and helpfulness of product reviews in a multicultural marketplace. Therefore, the present research identifies how review subjectivity explains the relationship between review sentiment and review helpfulness in individualistic (i.e., the U.S.) and collectivistic (i.e., India) cultures. By means of two studies, the first using secondary data collected from Amazon.com and the second a controlled experiment setting, we find that review subjectivity mediates the influence of review sentiments only in individualistic cultures such as the U.S., but not in collectivistic cultures like India. Furthermore, we find that the moderated mediation is evident only when comparing positive and negative sentiments. This research has implications for academic and industry practitioners in terms of incorporating culture in decisions on review helpfulness.
Biotransformation of Sclareol by a Fungal Endophyte of Salvia sclarea
Authors: Diao Mengxue , Li Chi , Lu Jian , Meng Lijun , Xie Nengzhong
Published: October 2023

Microbial endophytes are known as versatile producers of useful metabolites, which have extensive applications in pharmacy, fragrance, agriculture and food. This study aims to screen sclareol‐biotransforming microorganisms from Salvia sclarea, an untapped source of diverse endophytes. In this study, 50 culturable endophytes were isolated from S. sclarea grown in Xinjiang using sclareol as the sole carbon source and screened for their potential to transform sclareol into analogues. A fungal endophyte, identified as the generally recognized as safe (GRAS) strain Aspergillus tubingensis, can produce labd‐14‐ene‐3β,8α,13β‐triol and 8α,13β‐dihydroxylabd‐14‐en‐3‐one from sclareol, involving hydroxylation and carbonylation at the C3 site. Structures of the two metabolites were elucidated by HR‐ESI‐MS and NMR analysis. S. sclarea was proven to be a good source of endophytes that are prospective producers of secondary metabolites with valuable chemical and biological properties. This study is the first report regarding the isolation of endophytes from S. sclarea.
Employment and workdays lost among spouses of cancer survivors: Intersection with gender across cancer treatment status
Authors: Litzelman Kristin , Han Xuesong , Zhao Jingxuan , Zheng Zhiyuan , Yabroff K. Robin
Published: October 2023

Background

Cancer patients and survivors have high care needs, often provided by a spouse or partner. The purpose of this study was to elucidate how employment and work loss patterns differed across cancer history/treatment status and gender.

Methods

Using nationally representative data from the Medical Expenditure Panel Survey (2011, 2016, and 2017), the authors linked data across married participants and categorized them by spouses’ cancer treatment status (no cancer history, on treatment for cancer, off treatment for cancer). Multivariable logistic and zero‐inflated negative binomial regressions were used to assess the associations among cancer history/treatment status, gender, and employment outcomes (employment status and workdays lost to care for self or others).

Results

For men, employment did not differ significantly by cancer history/treatment status (on treatment: odds ratio [OR], 0.58; 95% confidence interval [CI], 0.33–1.02, off treatment: OR, 0.84; 95% CI, 0.62–1.14 vs. no cancer history). For women, employment was not significantly different when the spouse was on treatment for cancer compared to no cancer history (OR, 0.78; 95% CI, 0.33–1.86]) but was significantly increased for women whose spouse was off treatment (OR, 1.39; 95% CI, 1.05–1.84). Among employed participants, women whose spouse was on cancer treatment were nine times more likely to take days off work to provide care (OR, 9.52; 95% CI, 3.94–23.03) and took more than three times as many days off to care for others (OR, 3.21; 95% CI, 2.07–4.97) as men whose spouse had no cancer history.

Conclusions

Wives of cancer survivors are at increased risk of work loss, with implications for their financial and psychological well‐being. Employers, policymakers, and clinicians have opportunities to support working caregivers.
Efficient Cellulose/Nano‐silver Composite Sheet Derived from Pineapple Leaves for Hydrogen Sulfide Detection
Authors: Thongboon Surached , Muenchanama Chattathip , Chanthanumatt Ravinnipa , Charoenchaitrakool Manop , Sudsakorn Kandis , Prapainainar Paweena , Roddecha Supacharee , Chareonpanich Metta , Faungnawakij Kajornsak , Seubsai Anusorn
Published: October 2023

Pineapple leaves, a raw agricultural waste biomass material, were used to synthesize microcrystalline cellulose (MCC) through extraction, bleaching, and hydrolysis. Then, the MCC was mixed with different concentrations of silver nitrate solution to create a regenerated cellulose composite sheet loaded with silver nanoparticles (AgNPs) and used as a hydrogen sulfide (H2S) detector. The physicochemical properties of the cellulose composite sheet loaded with AgNPs before and after H2S exposure were analyzed using various advanced equipment. The H2S adsorption experiments revealed that the composite sheet underwent a visible change from yellow to brown upon exposure to H2S gas. The range for accurate prediction of the H2S concentration was 20–50 ppm. When temperature in the surroundings of the composite sheet was lower and the H2S gas concentration was higher, the color became darker (dark brown). The relative humidity conditions rarely impacted the sensitivity of color change in the cellulose composite sheet. The stability experiment showed that the cellulose composite sheet had exceptional stability at storage temperatures of 4 and 25 °C for 30 days. This composite sheet mixed with AgNPs has the potential to be used as a gas test strip to detect H2S, such as in food packaging.
Enhancing the Properties of Self‐Healing Gelatin Alginate Hydrogels by Hofmeister Mediated Electrostatic Effect
Authors: Das Sougat , Majumdar Saptarshi
Published: October 2023

The cross‐linker‐free hydrogels have gained attention due to their lack of need for chemically modified polymers, resulting in better biocompatibility. The hydrogel properties can be enhanced by altering physical forces such as electrostatics and H‐bonds. Tuning the physical interactions between polymers, salts, and plasticisers can unlock new horizons in material properties. This article examines four different salts and mixtures to determine their impact on gelatin‐alginate biomaterial design. Drug release, swelling, and rheological properties are represented using a 3‐D plot, and optimum samples are identified. It is concluded that kosmotropes yield better release and swelling results than chaotropes. The physical interactions of these salts with polymers are explained using DLS and FTIR/ATR studies, and these findings are corroborated with release, swelling, and rheological analyses. Another aspect of the biomaterial, self‐healing property, is also considered. A 3‐D plot is prepared using release kinetics, gel strength, and recovery percentage (three important factors for self‐healing hydrogels). Chaotropes are identified as better candidates for self‐healing behaviour. However, when considering gel strength, release, and self‐healing, kosmotropes are favourable. Hence, different salts can be selected based on the desired application for hydrogels. It is also concluded that electrostatic forces hinder the formation of H‐bonds between polymer chains.
Insights on the Anion Effect in N‐heterocyclic Carbene Based Dinuclear Gold(I) Catalysts
Authors: Campagnolo Filippo , Bevilacqua Matteo , Baron Marco , Tubaro Cristina , Biffis Andrea , Zuccaccia Daniele
Published: October 2023

Dinuclear bisNHC (bis(N‐heterocyclic carbene)) gold(I) complexes 3 a and 4 a of general formula [Au2Br2(bisNHC)] were tested as catalysts in the cycloisomerization of N‐(prop‐2‐yn‐1‐yl)benzamide and in the hydromethoxylation of 3‐hexyne in the presence of silver(I) activators bearing different counteranions. The catalytic performance of mononuclear NHC complexes (1 a, 2 a) in the same reactions was also studied. The results highlighted the fundamental role of both NHC ligand and counterion in the catalytic cycles and activation process: dinuclear catalysts exhibit higher initial activity even under milder conditions but suffer in terms of stability with respect to mono NHCs. Furthermore, a new dinuclear bisNHC gold(I) complex 4 b of general formula [Au2(OTs)2(bisNHC)] (OTs=p‐toluenesulfonate) was successfully synthesized and characterized by means of NMR and ESI‐MS analyses.
Thixotropic Hydrogels Based on Laponite® and Cucurbituril for Delivery of Lipophilic Drug Molecules
Authors: Massaro Marina , Cinà Giuseppe , Borrego‐Sánchez Ana , Sainz‐Díaz C. Ignacio , Viseras‐Iborra César , Sánchez‐Espejo Rita , de Melo Barbosa Raquel , Leone Federica , Pibiri Ivana , Noto Renato , Riela Serena
Published: October 2023

Invited for this month's cover are the collaborating groups of Prof. Serena Riela at University of Catania, Prof. César Viseras at University of Granada and Dr. Ignacio Sainz‐Diaz at Instituto Andaluz de Ciencias de la Tierra. The cover picture shows the possible application of the developed system. In particular, flufenamic acid, anti‐inflammatory and anti‐pyretic drug, was complexed into cucurbituril cavity and the supramolecular system obtained was used as filler for laponite® hydrogel for its topical delivery. More information can be found in the Research Article by Viseras‐Iborra, Riela, and co‐workers.
Dissecting wireless body area networks routing protocols: Classification, comparative analysis, and research challenges
Authors: Narwal Bhawna , Malik Monica , Mohapatra Amar Kumar , Baliyan Niyati , Shukla Varun , Kumar Manoj
Published: October 2023

In the present scenario, wireless body area network (WBAN) use case has gone beyond medical monitoring (e.g., E‐Healthcare) and has become a vital part of our daily lives. WBANs, applied in E‐Healthcare systems, extract the physiological parameters through the implanted (in‐body) and/or wearable (on‐body) sensors applied to the human body and route them to the remote server in a systematized and well‐grounded manner. Thus, routing is the most primitive and non‐trivial task in WBANs for prompt and proper delivery of sensed data. The design of routing protocol is crucial for efficacious communication and high network performance. Therefore, the target of this paper is to present an all‐encompassing taxonomy of the state‐of‐the‐art routing protocols in WBANs. Firstly, this paper provides an insight into WBANs and their related projects. Next, WBAN routing challenges are explored, and after clustering these challenges based on their operating mechanism, the routing protocols are categorized into eight categories, which correspond to cluster‐ and tree‐based, cross‐layer‐based, fuzzy‐based, interference‐based, posture‐based, QoS‐based, SDN‐based, and temperature‐based routing protocols. Furthermore, comparison tables highlighting the goals, strengths, limitations, and novelty of each protocol, along with a qualitative comparison table of the routing protocols for each category based on their features are furnished. This exhaustive survey can serve as a starting point for WBAN researchers, as open research issues have been highlighted in the discussion section.
Improving clinical efficiency in screening for cognitive impairment due to Alzheimer's
Authors: Ren Yueqi , Shahbaba Babak , Stark Craig E. L.
Published: October 2023

INTRODUCTION

To reduce demands on expert time and improve clinical efficiency, we developed a framework to evaluate whether inexpensive, accessible data could accurately classify Alzheimer's disease (AD) clinical diagnosis and predict the likelihood of progression.

METHODS

We stratified relevant data into three tiers: obtainable at primary care (low‐cost), mostly available at specialty visits (medium‐cost), and research‐only (high‐cost). We trained several machine learning models, including a hierarchical model, an ensemble model, and a clustering model, to distinguish between diagnoses of cognitively unimpaired, mild cognitive impairment, and dementia due to AD.

RESULTS

All models showed viable classification, but the hierarchical and ensemble models outperformed the conventional model. Classifier “error” was predictive of progression rates, and cluster membership identified subgroups with high and low risk of progression within 1.5 to 3 years.

DISCUSSION

Accessible, inexpensive clinical data can be used to guide AD diagnosis and are predictive of current and future disease states.

HIGHLIGHTS

Classification performance using cost‐effective features was accurate and robust

Hierarchical classification outperformed conventional multinomial classification

Classification labels indicated significant changes in conversion risk at follow‐up

A clustering‐classification method identified subgroups at high risk of decline