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Kun-Ming Chan,1 Yin Lai,1 Hao-Chien Hung,1 Jin-Chiao Lee,1 Chih-Hsien Cheng,1 Yu-Chao Wang,1 Tsung-Han Wu,1 Chen-Fang Lee,1 Ting-Jung Wu,1 Hong-Shiue Chou,1 Ching-Ting Wang,2 Pei-Mei Chai,2 Hsin-Yi Lien,3 Wei-Chen Lee1 1Department of General Surgery and Chang Gung Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan; 2Department of Nursing, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan; 3Graduate School of Education, Ming Chuan University, Taoyuan, TaiwanCorrespondence: Kun-Ming Chan, Department of General Surgery and Chang Gung Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, No. 5 Fu-Hsing Street, Gui-Shan District, Taoyuan City, 33305, Taiwan, Tel +886-3-3281200 Ext 3366, Fax +886-3-3285818, Email chankunming@cgmh.org.twBackground: Tyrosine kinase inhibitors (TKIs) remain the primary therapeutic option for patients with advanced-stage hepatocellular carcinoma (HCC). However, the selection of a suitable TKI is an issue in real-world clinical practice. Thus, this study aimed to identify patients most likely to benefit from lenvatinib treatment.Methods: A retrospective review of 143 patients with unresectable advanced-stage HCC treated with lenvatinib between January 2020 and December 2021 was performed. Outcomes related to lenvatinib treatment were measured, and the clinical parameters affecting prognosis were analyzed.Results: Overall, the median time of progression-free survival (PFS) and overall survival (OS) were 7.1 months and 17.7 months, respectively. Prognostic analyses found that Child-Pugh score > 5 (hazard ratio [HR] = 2.43, 95% confidence interval [CI] = 1.55– 3.80, p = 0.001) was a significant factor affecting the PFS of HCC after lenvatinib treatment. Child-Pugh score > 5 (HR = 2.12, 95% CI = 1.20– 3.74, p = 0.009), body weight ≥ 60 kg (HR = 0.54, 95% CI = 0.32– 0.90, p = 0.020), and additional trans-arterial chemoembolization (TACE) treatment (HR = 0.38, 95% CI = 0.21– 0.70, p = 0.003) were significant prognostic factors for OS. However, early α-fetoprotein reduction was not significantly correlated with patient outcomes. Additionally, patients with pre-treatment neutrophil-lymphocyte ratio > 4.07 showed a significant worse PFS and OS than other patients.Conclusion: The outcome of patients with advanced-stage HCC remains poor. However, the host condition, including good physical status and better functional liver preservation, largely affected the outcome of patients receiving lenvatinib treatment. Moreover, additional locoregional therapy for intrahepatic HCC, other than TKI treatment, can be considered in certain patients to achieve a favorable outcome.Keywords: hepatocellular carcinoma, advanced-stage, tyrosine kinase inhibitor, lenvatinib, outcome

To compare the outcomes of patients requiring extracorporeal membrane oxygenation (ECMO) support who had a restrictive transfusion strategy with those who had a liberal strategy.We retrospectively reviewed all adult patients from 2010 to 2019 who received a minimum of one packed red blood cell (pRBC) during ECMO. Hemoglobin values before each transfusion were retrieved. Restrictive transfusion strategy was defined as a transfusion threshold ≤8.5 g/dl in all transfusion episodes for a single patient, while liberal transfusion strategy was defined as a transfusion threshold8.5 g/dl in any transfusion episode.The analysis included 763 patients, with 138 (18.1%) patients in the restrictive and 625 (81.9%) in the liberal transfusion strategy group. The median hemoglobin level, taking into account all measured hemoglobin values, during ECMO support was 8.3 and 9.9 g/dl, and the average units of pRBC received per day were 0.7 (0.3-1.8) and 1.2 (0.6-2.3), respectively. There were no significant differences in intensive care unit (ICU) mortality (adjusted odds ratio (OR), 0.86; 95% CI 0.56-1.30; p = .47), hospital mortality (adjusted OR, 0.79; 95% CI 0.52-1.21; p = .28), and 90-day mortality (adjusted OR, 0.84; 95% CI 0.55-1.28; p = .42) between the two groups. Among subgroup analyses, a restrictive transfusion strategy was associated with decreased risk of ICU mortality in patients on veno-venous ECMO (adjusted OR, 0.36; 95% CI 0.17-0.73; p = .005). There was no heterogeneity on outcomes across patients stratified by age, APACHE IV score, or need for large volume transfusion.Our data suggested it may be safe to adopt a restrictive red cell transfusion threshold of 8.5 g/dl in patients on ECMO, and highlighted the need for prospective trials in this heavily-transfused population.

Infants with genital development considered atypical for assigned female sex may undergo feminizing genitoplasty (clitoroplasty and/or vaginoplasty) in early life. We sought to identify factors associated with parent/caregiver decisions regarding genitoplasty for their children with genital virilization.Longitudinal, observational study SETTING: Twelve pediatric centers in the United States with multidisciplinary differences/disorders of sex development clinics, 2015-2020 PARTICIPANTS: Children under 2 years old with genital appearance atypical for female sex of rearing and their parents/caregivers INTERVENTIONS/OUTCOME MEASURES: Data on the child's diagnosis and anatomic characteristics before surgery were extracted from the medical record. Parents/caregivers completed questionnaires on psychosocial distress, experience of uncertainty, cosmetic appearance of their child's genitalia, and demographic characteristics. Urologists rated cosmetic appearance. For 58 patients from the study cohort with genital virilization being raised as girls or gender-neutral, we compared these data across 3 groups based on the child's subsequent surgical intervention: (i) no surgery (n = 5), (ii) vaginoplasty without clitoroplasty (V-only) (n = 15), and (iii) vaginoplasty and clitoroplasty (V+C) (n = 38).Fathers' and urologists' ratings of genital appearance were more favorable in the no-surgery group than in the V-only and V+C groups. Clitorophallic length was greater in the V+C group compared with the V-only group, with substantial overlap between groups. Mothers' depressive and anxious symptoms were lower in the no-surgery group compared with the V-only and V+C groups.Surgical decisions were associated with fathers' and urologists' ratings of genital appearance, the child's anatomic characteristics, and mothers' depressive and anxious symptoms. Further research on surgical decision-making is needed to inform counseling practices.

Background: The therapeutic efficacy of dendritic cell (DC)-immunotherapy for large hepatoma in mice is unsatisfactory. Materials & methods: DC-based immunotherapy was used to treat Hepa1-6 tumors measuring 6 ± 1 mm in diameter, enhanced by boosting tumor antigens. Results: CD4+ and CD8+ T-cells were contracted and transformed into memory phenotypic cells after DC-based vaccination. When T-cells were re-stimulated, T-cells obtained from mice boosted by tumor antigen injection showed highest proliferation capacity. When mice with large tumors were treated, DC-based vaccination boosted by tumor antigen and an additional DC-infusion yielded curative rates of 50% and 23.1%, respectively. Conclusion: DC vaccination induced effector memory cells. Antigen presentation recalled by DC or tumor antigens increased the curative rate in mice with large tumors.

This study aims to identify independent factors associated with cervical spinal injuries in head-injured patients. The extent of injuries to other body parts was assessed by the Abbreviated Injury Scale (AIS) and was included in the analysis.Consecutive head-injured patients admitted via the emergency department from January 1, 2014 to December 31, 2016 were retrospectively reviewed. The inclusion criteria were head-injured patients with an Abbreviated Injury Scale (AIS) score ≥2 (i.e., head injuries with intracranial hematoma or skull fracture). Patients with minor head injuries with only scalp abrasions or superficial lacerations without significant intracranial injuries (i.e., head injury AIS score = 1) were excluded. The primary outcome was to identify independent predictors associated with cervical spinal injuries in these head-injured patients. Univariate and multivariable analyses were conducted.A total of 1105 patients were identified. Of these patients, 11.2% (n = 124) had cervical spinal injuries. Univariate and multivariable analyses identified male gender (P = 0.006), the presence of thoracic injury (including rib fracture, hemothorax, or pneumothorax) (P = 0.010), and hypotension with systolic blood pressure90 mm Hg on admission (P = 0.009) as independent predictors for cervical spinal injury in head-injured patients.This study showed that about 1 in 10 patients with significant head injury had cervical spine injury, usually associated with fracture or dislocation. Male gender, the presence of thoracic injury, and hypotension on admission were independent risk factors associated with cervical spinal injuries.

Reverse end-to-side (RETS) nerve transfer has become increasingly popular in patients with severe high ulnar nerve injury, but the reported outcomes have been inconsistent.To evaluate the "babysitting effect," we compared outcomes after anterior interosseous nerve RETS transfer with nerve decompression alone. To evaluate the source of regenerating axons, a group with end-to-end (ETE) transfer was used for comparisons.Electrophysiology measures were used to quantify the regeneration of anterior interosseous nerve (AIN) and ulnar nerve fibers while functional recovery was evaluated using key pinch and Semmes-Weinstein monofilaments. The subjects were followed postsurgically for 3 years.Sixty-two subjects (RETS = 25, ETE = 16, and decompression = 21) from 4 centers in Western Canada were enrolled. All subjects with severe ulnar nerve injury had nerve compression at the elbow except 10 in the ETE group had nerve laceration or traction injury. Postsurgically, no reinnervation from the AIN to the abductor digiti minimi muscles was seen in any of the RETS subjects. Although there was no significant improvement in compound muscle action potentials amplitudes and pressure detection thresholds in the decompression and RETS group, key pinch strength significantly improved in the RETS group ( P.05).The results from published clinical trials are conflicting in part because crossover regeneration from the donor nerve has never been measured. Unlike those with ETE nerve transfers, we found that there was no crossover regeneration in the RETS group. The extent of reinnervation was also no different from decompression surgery alone. Based on these findings, the justifications for this surgical technique need to be carefully re-evaluated.

The role of afferent feedback and central motor drive in muscle activation has a profound impact on our understanding of movement control in health and disease. Dr. Richard B. Stein was a pioneer who made major contributions to the field. In addition to fundamental discoveries using animal models, he translated this to the clinic to benefit patients with spinal cord and other neurological injuries. Along the way, he inspired a generation of scientists around the world.

Background Early antiviral therapy was effective in the treatment of coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of combined interferon beta-1b and remdesivir treatment in hospitalized COVID-19 patients. Methods We conducted a multicentre, prospective open-label, randomized-controlled trial involving high-risk adults hospitalized for COVID-19. Patients were randomly assigned to a 5-day interferon beta-1b 16 million units daily and remdesivir 200 mg loading on day 1 followed by 100 mg daily on day 2 to 5 (combination group), or to remdesivir only of similar regimen (control group) (1:1). The primary endpoint was the time to complete alleviation of symptoms (NEWS2 = 0). Results Two-hundred and twelve patients were enrolled. The median days of starting treatment from symptom onset was 3 days. The median age was 65 years, and 159 patients (75%) had chronic disease. The baseline demographics were similar. There was no mortality. For the primary endpoint, the combination group was significantly quicker to NEWS2 = 0 (4 vs 6.5 days; hazard ratio [HR], 6.59; 95% confidence interval [CI], 6.1–7.09; P < .0001) when compared to the control group. For the secondary endpoints, the combination group was quicker to negative nasopharyngeal swab (NPS) viral load (VL) (6 vs 8 days; HR, 8.16; 95% CI, 7.79–8.52; P < .0001) and to develop seropositive immunoglobulin G (IgG) (8 vs 10 days; HR, 10.78; 95% CI, 9.98–11.58; P < .0001). All adverse events resolved upon follow-up. Combination group (HR, 4.1 95% CI, 1.9–8.6, P < .0001) was the most significant independent factor associated with NEWS2 = 0 on day 4. Conclusions Early treatment with interferon beta-1b and remdesivir was safe and better than remdesivir only in alleviating symptoms, and in shortening viral shedding and hospitalization with earlier seropositivity in high-risk COVID-19 patients. Clinical Trials Registration NCT04647695.

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) increases afterload to the injured heart and may hinder myocardial recovery. We aimed to compare the sensitivity of left ventricular (LV) systolic function to the afterload effects of peripheral V-A ECMO during the acute and delayed stages of acute myocardial dysfunction.A total of 46 adult patients who were supported by peripheral V-A ECMO between April 2019 and June 2021 were analysed. Serial cardiac performance parameters were measured by transthoracic echocardiography (TTE) on mean day 1 ± 1 of V-A ECMO initiation (n = 45, 'acute phase') and mean day 4 ± 2 of V-A ECMO initiation (n = 36, 'delayed phase'). Measurements were obtained at 100%, 120%, and 50% of ECMO target blood flow (TBF). LV global longitudinal strain (GLS) significantly improved from -6.1 (-8.9 to -4.0)% during 120% TBF to -8.8 (-11.5 to -6.0)% during 50% TBF (P 0.001). The sensitivity of LV GLS to changes in ECMO flow was significantly greater in the acute phase of myocardial injury compared with the delayed phase [median (IQR) percentage change: 72.7 (26.8-100.0)% vs. 22.5 (14.9-43.8)%, P 0.001]. Findings from other echocardiographic parameters including LV ejection fraction [43.0 (29.1-56.8)% vs. 22.8 (9.2-42.2)%, P = 0.012] and LV outflow tract velocity-time integral [45.8 (18.6-58.7)% vs. 24.2 (12.6-34.0)%, P = 0.001] were similar. A total of 24 (52.2%) patients were weaned off ECMO successfully.We demonstrated that LV systolic function was significantly more sensitive to the afterload effects of V-A ECMO during the acute stage of myocardial dysfunction compared with the delayed phase. Understanding the evolution of the heart-ECMO interaction over the course of acute myocardial dysfunction informs the clinical utility of echocardiographic assessment in patients on V-A ECMO.

It is important to quantify the amount of crossover innervation from the anterior interosseous nerve (AIN) through Martin-Gruber anastomosis (MGA) particularly in patients with high ulnar nerve injury who undergo nerve transfer surgery. The objective of this study is to describe a novel electrophysiological method for quantifying innervation from the AIN that can be done using conventional nerve conduction study setup and commonly available software for analysis.Seven subjects with MGA and nine patients who had undergone AIN to ulnar nerve transfer underwent conventional motor nerve conduction studies. Recording was done over the hypothenar and first dorsal interosseous muscles while stimulating the median and ulnar nerves at the wrist and elbow. Datapoint-by-datapoint subtraction of the compound muscle action potentials evoked at the elbow and wrist was performed after they had been onset-aligned. The results were compared to the collision technique and innervation ratio method.Results from the digital subtraction method were highly correlated with the collision technique (r = 0.96, p 0.05). In contrast, its correlation with the innervation ratio method is substantially lower.In comparison to previously described techniques, the digital subtraction method has a number of practical advantages. It uses conventional nerve conduction study setup, and the added step of digital alignment and subtraction can be done through commonly available software. With the increasing use of nerve transfer surgery in severe high ulnar nerve injury, this could be a useful method to identify the presence of MGA prior to surgery and for evaluating nerve recovery following surgery.

BACKGROUND: The utilization of extracorporeal membrane oxygenation (ECMO) has increased rapidly around the world. Being an overall low-volume high-cost form of therapy, the effectiveness of having care delivered in segregated units across a geographical locality is debatable. METHODS: All adult extracorporeal membrane oxygenation cases admitted to public hospitals in Hong Kong between 2010 and 2019 were included. “High-volume” centers were defined as those with >20 extracorporeal membrane oxygenation cases in the respective calendar year, while “low-volume” centers were those with ≤20. Clinical outcomes of patients who received extracorporeal membrane oxygenation care in high-volume centers were compared with those in low-volume centers. RESULTS: A total of 911 patients received extracorporeal membrane oxygenation—297 (32.6%) veno-arterial extracorporeal membrane oxygenation, 450 (49.4%) veno-venous extracorporeal membrane oxygenation, and 164 (18.0%) extracorporeal membrane oxygenation-cardiopulmonary resuscitation. The overall hospital mortality was 456 (50.1%). The annual number of extracorporeal membrane oxygenation cases in high- and low-volume centers were 29 and 11, respectively. Management in a high-volume center was not significantly associated with hospital mortality (adjusted odds ratio (OR) 0.86, 95% confidence interval (CI): 0.61–1.21, P=0.38), or with intensive care unit mortality (adjusted OR 0.76, 95% CI: 0.54–1.06, P=0.10) compared with a low-volume center. Over the 10-year period, the overall observed mortality was similar to the Acute Physiology And Chronic Health Evaluation IV-predicted mortality, with no significant difference in the standardized mortality ratios between high- and low-volume centers (P=0.46). CONCLUSIONS: In a territory-wide observational study, we observed that case volumes in extracorporeal membrane oxygenation centers were not associated with hospital mortality. Maintaining standards of care in low-volume centers is important and improves preparedness for surges in demand.

BackgroundAdolescents, especially the socioeconomically disadvantaged, are facing devastating psychosocial impact of the COVID-19 pandemic during their critical developmental period. This study aims to (i) examine the socioeconomic patterning of the worsening of psychosocial wellbeing, (ii) delineate the underlying mediating factors (i.e., overall worry about COVID-19, family's financial difficulty, learning problems, and loneliness), and (iii) explore the moderating effect of resilience in the inter-relationship among adolescents under COVID-19.MethodsBased on maximum variation sampling of 12 secondary schools of diverse socioeconomic background in Hong Kong, 1018 students aged 14-16 years were recruited and completed the online survey between September and October 2021. Multi-group structural equation modeling (SEM) by resilience levels was employed to delineate the pathways between socioeconomic position and the worsening of psychosocial wellbeing.ResultsSEM analysis showed a significant total effect of socioeconomic ladder with the worsening of psychosocial wellbeing during the pandemic in the overall sample (β = −0.149 [95% CI = −0.217 – −0.081], p < 0.001), which operated indirectly through learning problems and loneliness (both p < 0.001 for their indirect effects). Consistent pattern with stronger effect size was observed in the lower resilience group; nonetheless, the associations were substantially mitigated in the higher resilience group.ConclusionIn addition to facilitating self-directed learning and easing loneliness during the pandemic, evidence-based strategies to build up resilience among adolescents are critical to buffer against the adverse socioeconomic and psychosocial impacts of the pandemic or other potential catastrophic events in the future.

Human social epigenomics research is critical to elucidate the intersection of social and genetic influences underlying racial and ethnic differences in health and development. However, this field faces major challenges in both methodology and interpretation with regard to disentangling confounded social and biological aspects of race and ethnicity. To address these challenges, we discuss how these constructs have been approached in the past and how to move forward in studying DNA methylation (DNAm), one of the best-characterized epigenetic marks in humans, in a responsible and appropriately nuanced manner. We highlight self-reported racial and ethnic identity as the primary measure in this field, and discuss its implications in DNAm research. Racial and ethnic identity reflects the biological embedding of an individual’s sociocultural experience and environmental exposures in combination with the underlying genetic architecture of the human population (i.e., genetic ancestry). Our integrative framework demonstrates how to examine DNAm in the context of race and ethnicity, while considering both intrinsic factors—including genetic ancestry—and extrinsic factors—including structural and sociocultural environment and developmental niches—when focusing on early-life experience. We reviewed DNAm research in relation to health disparities given its relevance to race and ethnicity as social constructs. Here, we provide recommendations for the study of DNAm addressing racial and ethnic differences, such as explicitly acknowledging the self-reported nature of racial and ethnic identity, empirically examining the effects of genetic variants and accounting for genetic ancestry, and investigating race-related and culturally regulated environmental exposures and experiences.

Background As the RNA secondary structure is highly related to its stability and functions, the structure prediction is of great value to biological research. The traditional computational prediction for RNA secondary prediction is mainly based on the thermodynamic model with dynamic programming to find the optimal structure. However, the prediction performance based on the traditional approach is unsatisfactory for further research. Besides, the computational complexity of the structure prediction using dynamic programming is $$O(N^3)$$ O ( N 3 ) ; it becomes $$O(N^6)$$ O ( N 6 ) for RNA structure with pseudoknots, which is computationally impractical for large-scale analysis. Results In this paper, we propose REDfold, a novel deep learning-based method for RNA secondary prediction. REDfold utilizes an encoder-decoder network based on CNN to learn the short and long range dependencies among the RNA sequence, and the network is further integrated with symmetric skip connections to efficiently propagate activation information across layers. Moreover, the network output is post-processed with constrained optimization to yield favorable predictions even for RNAs with pseudoknots. Experimental results based on the ncRNA database demonstrate that REDfold achieves better performance in terms of efficiency and accuracy, outperforming the contemporary state-of-the-art methods.

Receptor-Interacting Protein Kinase 1 (RIPK1) and RIPK3 are signaling adaptors that critically regulate cell death and inflammation. Tumors have adapted to subvert RIPK-dependent cell death, suggesting that these processes play key roles in tumor regulation. Moreover, RIPK-driven cancer cell death may bolster durable anti-tumor immunity. On the other hand, there are examples in which RIPKs induce inflammation and aid tumor progression. Furthermore, the RIPKs can exert its effect on tumor growth through regulating the activity of immune effectors in the tumor microenvironment, thus highlighting the context-dependent roles of RIPKs. Here, we review recent advances on the regulation of RIPK activity in tumors and immune cells and how these processes coordinate with each other to control tumorigenesis.

Suprasellar germinomas can present with non-diagnostic, or even normal results on imaging. The spectrum of reported cases ranges from normal imaging, thickened pituitary stalks, to discrete tumour growths. This similar phenomenon is less commonly seen in the pineal region, or bifocal germinomas, and the literature is sparse with only a few case series or reports mentioning a similar presentation of signs and symptoms preceding radiological evidence of diagnosis. We report a case of pineal germinoma presenting with dorsal midbrain syndrome with no evidence of tumour growth on initial imaging despite symptoms. For patients presenting with this clinical radiological latent period, follow-up imaging is useful to identify interval development of germinomas. This applies to patients with dorsal midbrain syndrome, or even other unexplained ophthalmoplegia, as the initial sign of pineal region germinoma, despite normal imaging.

To compare the dosimetric performance of Intensity Modulated Proton Therapy (IMPT) and Intensity Modulated Radiotherapy (IMRT) in terms of target volume coverage and sparing of neurological organs-at-risk (OARs) in salvaging recurrent nasopharyngeal carcinoma (rNPC). The maximum dose to the internal carotid artery (ICA) and nasopharyngeal (NP) mucosa, which are associated with potential carotid blowout and massive epistaxis, were also evaluated.IMRT and IMPT treatment plans were created for twenty patients with locally advanced rNPC. Planning Target Volume (PTV) was used to account for the setup and spatial error/uncertainty in the IMRT planning. Robust optimization on Clinical Target Volume (CTV) coverage with consideration of range and setup uncertainty was employed to produce two IMPT plans with 3-field and 4-field arrangements. The planning objective was to deliver 60 Gy to the PTV (IMRT) and CTV (IMPT) without exceeding the maximum lifetime cumulative Biologically Effective Dose (BED) of the neurological OARs (applied to the Planning organs-at-risk volume). The target dose coverage as well as the maximum dose to the neurological OARs, ICA, and NP mucosa were compared.Compared with IMRT, 3-field IMPT achieved better coverage to GTV V100% (83.3% vs. 73.2%, P0.01) and CTV V100% (80.5% vs. 72.4%, P0.01), and lower maximum dose to the critical OARs including the spinal cord (19.2 Gy vs. 22.3 Gy, P0.01), brainstem (30.0 Gy vs. 32.3 Gy, P0.01) and optic chiasm (6.6 Gy vs. 9.8 Gy, P0.01). The additional beam with the 4-fields IMPT plans further improved the target coverage from the 3-field IMPT (CTV V98%: 85.3% vs. 82.4%, P0.01) with similar OAR sparing. However, the target dose was highly non-uniform with both IMPT plans, leading to a significantly higher maximum dose to the ICA (∼68 Gy vs. 62.6 Gy, P0.01) and NP mucosa (∼72 Gy vs. 62.8 Gy, P0.01) than IMRT.IMPT demonstrated some dosimetric advantage over IMRT in treating rNPC. However, IMPT could also result in very high dose hot spots in the target volume. Careful consideration of the ICA and NP mucosal complications is recommended when applying IMPT on rNPC patients.

Objective: Network typology studies have identified heterogeneous types of older adults’ social networks. However, little is known about stability and change in social network types over time. We investigate transitions in social network types among older adults, aged 60 years and older, and factors associated with such transitions. Methods: We used data on 1,305 older adults, participating in 2 waves of a national, longitudinal survey, conducted in 2016–2017 and 2019, in Singapore. Latent transition analysis identified the distinct types of social networks and their transition patterns between the waves. Multinomial logistic regression examined the association of baseline and change in physical, functional, and mental health and baseline sociodemographic characteristics with network transitions into more diverse or less diverse types. Results: We found 5 social network types at both waves, representing the most to the least diverse types – diverse, unmarried and diverse, extended family, immediate family, and restricted. Between waves, about 57% of respondents retained their social network type, whereas 24% transitioned into more diverse types and 19% into less diverse types. Those who were older and less educated and those with worsening functional and mental health were more likely to transition into less diverse types versus remaining in the same type. Discussion: The findings capture the dynamics in social network composition among older adults in the contemporary aging society. We highlight sociodemographic and health disparities contributing to later life social network diversity.

Objective To provide better preconceptional and prenatal counselling to patients with sjögren syndrome (SS). Methods In total, 2 100 143 pregnancies between 2004 and 2014 were identified in the Taiwan National Health Insurance database and birth registry. The maternal history of SS was ascertained, and data were compared between pregnant women with and without SS. We assessed the odds ratios and 95% CIs of fetal–neonatal and maternal outcomes. Results There were 449 pregnancies in women with SS and 2 099 694 pregnancies in women without SS. The risks of still birth [odds ratio (OR) = 2.14, 95% CI = 1.01, 4.55], low birth weight ( Conclusion Women with SS have significant risks of adverse fetal–neonatal and maternal outcomes and must undergo prenatal counselling to understand the risks involved before conception.

Supplemental material, sj-docx-1-psw-10.1177_14789299221147460 for Cooperate But Divided at Heart: Analysis of an Opposition Elite Survey During Autocratization by Au Nok Hin, Chan Ka Ming and Ng Ka Lun in Political Studies Review

OBJECTIVE: Fertility-related health care and decision-making needs for youth with differences of sex development (DSD) are complex and vary by condition and the values and preferences of each individual and their partner and/or family. Discussing fertility implications can be a challenging aspect of clinician and family communication about a DSD diagnosis. This qualitative study assesses fertility-related communication experiences of adolescents and young adults (AYA) with DSD. METHOD: Participants included 97 AYA with DSD ages 12–26 years (M = 18.5, SD = 3.9) who completed questionnaires on demographic and medical information and patient–clinician communication. A subsample of 33 AYA also completed semistructured interviews about experiences with fertility discussions. RESULTS: Two major themes, each with subthemes, were identified: (1) understanding of fertility related to (1a) one’s own fertility status, (1b) reproductive and parenting options, and (1c) emotional reactions to one’s own fertility status and (2) conversations about fertility related to (2a) reflections on conversations, (2b) barriers, and (2c) advice. CONCLUSIONS: AYA perspectives in this study provide important information about how youth with DSD learn about their fertility status, the impact their fertility status has on them, and the fertility-related conversations they have with their providers and families. Specific recommendations for providers and parents or caregivers include the following: inform youth of their fertility status as early as possible; be direct but patient in delivering information; begin by giving basic information and provide more detail as the conversation unfolds; revisit the conversation over time to allow for further discussion or information-seeking; offer additional information or resources, including behavioral health resources.

This study is initiated by the increasing use of steel tubular members with octagonal hollow sections (OctHSs) in civil structures. Previous studies primarily focused on the local buckling behaviour of cold-formed steel OctHSs. However, investigations on the global buckling behaviour of OctHS long columns remain scarce. Thus, the main objective of this paper is to numerically investigate the structural performance of the OctHS columns. A finite element method (FEM) was developed for tubular columns and validated against relevant experimental results reported in the literature. Subsequently, a parametric study on 239 OctHS columns was carried out. The applicability of design methods outlined in Eurocode 3, ANSI/AISC 360-16 and ASCE/SEI 48-19 was evaluated. The evaluation shows that the design method in Eurocode 3 provides conservative predictions for the load-bearing capacity of OctHS columns, while the ANSI/AISC 360-16 design method was slightly unconservative for the strength predictions. The design method in ASCE/SEI 48-19 gave inaccurate predictions for the load-bearing capacity of the OctHS columns. Modifications to the design methods in ANSI/AISC 360 and ASCE/SEI 48-19 were proposed to improve the accuracy of strength predictions and to obtain safe structural designs. The reliability of the design method in Eurocode 3 and the modified American design methods was assessed through the reliability analysis and found to satisfy the reliability requirements.

IntroductionKimura’s disease (KD) is an uncommon lymphoproliferative fibroinflammatory disorder. Patients present with head and neck subcutaneous nodules with or without lymphadenopathy. Peripheral blood eosinophilia and elevated serum immunoglobulin E (IgE) levels are typical. This study was designed to delineate the clinicopathological features, pattern of care, and disease course of 23 Taiwanese patients with KD.MethodsWe retrospectively analyzed the clinical data of 23 consecutive cases (16 male and 7 female; age at diagnosis: 12–77 years) of KD diagnosed at our institution from 2015 to 2020.ResultsThe median time from presentation to diagnosis was 1 month. Twenty-one patients presented with unilateral or bilateral head and neck masses. The remaining two presented with right flank and right arm lesions, respectively. Peripheral blood eosinophilia was observed in nine, and elevated IgE levels were observed in four. All were diagnosed using either excisional or core-needle biopsy. Seven patients underwent fine needle aspiration without a diagnostic yield. Salivary gland and lymph node involvement was observed in three and seven patients, respectively. Most lesions showed tissue eosinophilia (100%) and florid follicular hyperplasia (78.26%). Three cases had histological KD-IgG4-RD overlap and three had comorbid IgG4-RD were recognized. Thirteen patients underwent surgical resection, one received adjuvant therapy, and two received prednisolone monotherapy.ConclusionKD should be considered in patients with subcutaneous masses, eosinophilia, and elevated IgE levels. Biopsy remains the gold standard of diagnosis. Increased recruitment of IgG4+ plasma cells is a common feature. Consideration of IgG4-RD in all KD patients may be prudent.

The addition of a nitrogen-based functional group to alkenes via a direct catalytic method is an attractive way of synthesizing value-added amides. The regioselective hydroamidation of unactivated alkenes is considered one of the easiest ways to achieve this goal. Herein, we report the NiH-catalyzed anti-Markovnikov intermolecular hydroamidation of unactivated alkenes enabled by using 2,9-dibutylphenathroline (diBuphen) as the ligand. This protocol provides a platform for the direct synthesis of over 90 structurally diverse N-alkyl amides using dioxazolones, which can be easily derived from abundant carboxylic acid feedstocks. This method succeeds for both terminal and internal unactivated alkenes and some natural products. Mechanistic studies including DFT calculations reveal an initial reversible insertion/elimination of the [NiH] to the alkene, followed by the irreversible amidation to furnish the N-alkyl amides. By crossover experiments and deuterium labeling studies, the observed anti-Markovnikov regioselectivities are suggested to be controlled by the sterical environment of the coupling reaction.

Objective To evaluate the diagnostic accuracy of frameless stereotactic brain biopsy, compare it with the current international standard, and review the era for improvement. Background The diagnostic accuracy of frameless stereotactic brain biopsy has been reported but there is limited literature focusing on the reasons for non-diagnostic cases.This is a retrospective analysis of consecutive, prospectively collected frameless stereotactic brain biopsy procedures from 2007 to 2020. We evaluated the diagnostic accuracy of the frameless stereotactic brain biopsy procedures using structurally-defined criteria. The biopsy result was classified as conclusive, inconclusive, or negative, based on the pathological, radiological, and clinical diagnosis concordance. For inconclusive or negative results, we further evaluated the preoperative planning and postoperative imaging to review the errors. A literature review for the diagnostic accuracy of frameless stereotactic biopsy was performed for the validity of our results. The objective of the study is to identify the causes of non-diagnostic results for future improvement.There were 106 patients with 109 biopsy procedures performed from 2007 to 2020. The conclusive diagnosis was reached in 103 (94.5%) procedures. The inconclusive diagnosis was noted in four (3.7%) procedures and the negative biopsy was yielded in two (1.9%) procedures. Symptomatic hemorrhage was noted in one patient (0.9%). There was no mortality case (0.0%) in our series. The registration error and inaccurate targeting occurred in three trigonal lesions (2.8%), sampling of the non-representative part of the lesion occurred in two cases (1.8%), and one biopsy (0.9%) for lymphoma was negative due to the commencement of steroids. The literature review suggested that our diagnostic accuracy under the structurally-defined diagnosis criteria was comparable with the published literature, while the causes for non-diagnostic cases were uniquely performed and summarized.The stereotactic biopsy is a safe procedure with high diagnostic accuracy only if meticulous preoperative planning and careful intraoperative registration is performed. The common pitfalls precluding a conclusive diagnosis are registration errors and biopsies at non-representative sites.