A 6-Item Family Resilience Scale (FRS6) for Measuring Longitudinal Trajectory of Family Adjustment.

Two studies were conducted in Hong Kong to validate a brief measure of family resilience based on the three-factor CPR model. The CPR model stipulates that family resilience comprises three major factors: Communication and Connectedness (C), Positive Framing (P), and External Resources (R). Study 1 abbreviated the 16-item Family Resilience Scale (FRS16) into six items (FRS6) with a parent sample in the community (N = 1270). Study 2 tested the validity of the FRS6 with a single parent sample (N = 336). The result of Study 1 suggests a dominant general family resilience factor structure with three distinct subfactors. The highest factor loading items from each of the three subfactors were retained in the six-item FRS6. The resultant FRS6 was internally consistent and related to various correlates in similar or better strengths as compared to the FRS16. The results of a separate sample in Study 2 indicated that the FRS6 demonstrated satisfactory internal reliability and correlated significantly with individual resilience, quality of life, anxiety, and depression in the expected directions. Both studies supported that the FRS6 is a psychometrically sound measure of family resilience and can be used in longitudinal studies that aim to chart the trajectory of family adjustment following life adversities.

Challenges and Implications for Menopausal Health and Help-Seeking Behaviors in Midlife Women From the United States and China in Light of the COVID-19 Pandemic: Web-Based Panel Surveys.

BACKGROUND: The global population of women of menopausal age is quickly increasing. The COVID-19 pandemic has led to an accelerated increase in the use of telehealth services, especially technological solutions targeting women's health. Understanding the factors behind midlife women's help-seeking behaviors amidst the pandemic will assist in the development of person-centered holistic telehealth solutions targeting menopausal and postreproductive health. OBJECTIVE: This study aimed to compare the factors underlying help-seeking for menopausal distress among midlife women in the United States and China. METHODS: We conducted 2 web-based panel surveys in the United States using Amazon Mechanical Turk and in China using Credamo between July and October 2022. A total of 1002 American and 860 Chinese women aged between 40 and 65 years took part in the survey. The survey was designed based on the Health Belief Model with questions related to their menopausal knowledge, perceived severity of menopausal symptoms, perceived susceptibility to menopausal distress, perceived benefits of help-seeking, perceived COVID-19- and non-COVID-19-related barriers against help-seeking, self-efficacy, and motivation to seek help. Structural equations models were fitted for the data using full information maximum likelihood to manage missing data. RESULTS: Knowledge was not directly related to help-seeking motivation in both samples. Among the Chinese sample, knowledge was negatively related to perceived severity but positively related to COVID-19-related barriers; in turn, higher perceived severity, benefits, COVID-19-related barriers, and self-efficacy and lower non-COVID-19-related barriers were related to more motivation to seek help. In the US sample, knowledge was negatively related to perceived severity, susceptibility, benefits, barriers (COVID-19- and non-COVID-19-related), and self-efficacy; in turn, higher self-efficacy, COVID-19-related barriers, and benefits were associated with more help-seeking motivation. The factors explained 53% and 45.3% of the variance of help-seeking motivation among the American and Chinese participants, respectively. CONCLUSIONS: This study revealed disparate pathways between knowledge, health beliefs, and the motivation for help-seeking among American and Chinese midlife women with respect to menopausal distress. Our findings show that knowledge may not directly influence help-seeking motivation. Instead, perceived benefits and self-efficacy consistently predicted help-seeking motivation. Interestingly, concern over COVID-19 infection was related to higher help-seeking motivation in both samples. Hence, our findings recommend the further development of telehealth services to (1) develop content beyond health education and symptom management that serves to enhance the perceived benefits of addressing women's multidimensional menopausal health needs, (2) facilitate patient-care provider communication with a focus on self-efficacy and a propensity to engage in help-seeking behaviors, and (3) target women who have greater midlife health concerns in the postpandemic era.

A minority of women of childbearing potential are tested for pregnancy before chemoimmunotherapy: an Australian cancer centre experience.

BACKGROUND: Chemotherapy is potentially harmful to a developing foetus, and there are limited data on the foetal impact of chemoimmunotherapy (CIT). Therefore, determining pregnancy status prior to initiation of CIT should be standard of care. AIMS: To determine how many women of childbearing age are tested for pregnancy prior to immunochemotherapy administration. METHODS: A retrospective chart review at a large Australian metropolitan cancer referral centre, including 304 women aged 18-51 years with a diagnosis of cancer receiving outpatient-based CIT between 1 May 2015 and 12 June 2020. We assessed the uptake of pregnancy screening and contraception counselling prior to and during first-line CIT. RESULTS: Only 17.3% of CIT cycles (n = 416) screened patients for pregnancy no more than 90 days prior to administration, and the median time between pregnancy screening and treatment was approximately 3 weeks. One patient with early breast cancer had a spontaneous miscarriage estimated at 3-4 weeks' gestation, and neither the patient nor the treating oncologist was aware of this event. This was also the only patient who had a pregnancy test beyond the first cycle of CIT during their treatment. CONCLUSIONS: Our results highlight a concerningly low rate of pregnancy screening in women of childbearing age receiving CIT. The implication of missing a positive pregnancy test in this group of women could result in foetal complications, accidental miscarriage, potential bleeding risks and avoidable psychosocial stress. This highlights the urgent need for guidelines to mandate pregnancy testing in women of childbearing age receiving CIT and evidence-based implementation tools.

The Associations between Obsessive Compulsive Personality Traits, Self-Efficacy, and Exercise Addiction.

Exercise addiction refers to maladaptive exercise patterns involving compulsivity and addiction-like behaviors. Exercise addiction has been found to relate to negative physical and mental health outcomes such as heart abnormalities, physical injuries, and interpersonal conflicts. Based on the social cognitive theory, this study investigated the extent to which the interplay of obsessive compulsive personality disorder (OCPD) traits and self-efficacy beliefs would influence the development and maintenance of exercise addiction. A total of 1228 college students in the United States responded to an online survey. Based on cut-off scores of the Revised Exercise Addiction Inventory, the prevalence estimates of exercise addiction were 4.0% for males and 1.8% for females. Results showed that males are more prone to exercise addiction than females. Also, OCPD traits and self-efficacy significantly predicted exercise addiction after controlling for age and sex. Self-efficacy acted as a moderator in influencing the relationship between OCPD traits and exercise addiction, especially for females. At high levels of self-efficacy, more OCPD traits were significantly associated with a higher risk of exercise addiction. However, at low levels of self-efficacy, there was no association between OCPD traits and exercise addiction. The findings suggest that public education and intervention for exercise addiction should attend to the interplay between personality factors and sex.

Very early life microbiome and metabolome correlates with primary vaccination variability in children.

IMPORTANCE: We show that simultaneous study of stool and nasopharyngeal microbiome reveals divergent timing and patterns of maturation, suggesting that local mucosal factors may influence microbiome composition in the gut and respiratory system. Antibiotic exposure in early life as occurs commonly, may have an adverse effect on vaccine responsiveness. Abundance of gut and/or nasopharyngeal bacteria with the machinery to produce lipopolysaccharide-a toll-like receptor 4 agonist-may positively affect future vaccine protection, potentially by acting as a natural adjuvant. The increased levels of serum phenylpyruvic acid in infants with lower vaccine-induced antibody levels suggest an increased abundance of hydrogen peroxide, leading to more oxidative stress in low vaccine-responding infants.

Immunochemotherapy for life-threatening haematological malignancies in pregnancy: a systematic review of the literature and cross-sectional analysis of clinical trial eligibility.

The management of potentially life-threatening malignancies in pregnancy is complicated by a lack of robust safety and efficacy evidence. This data shortage stems from a historical exclusion of women of childbearing potential from prospective clinical trials due to concerns around potential teratogenicity and toxicity of investigational agents. We conducted a systematic review of published data on immunochemotherapeutic treatment of life-threatening haematological malignancies in pregnancy between 2010 and 2022, and the maternal and neonatal outcomes. We then performed a cross-sectional observational study of clinical trial protocols on ClinicalTrials.gov, between 2016 and 2022, recruiting women of childbearing potential with potentially life-threatening haematological malignancies, collecting trial demographic data, and documenting whether pregnant or lactating women were explicitly excluded, along with the type and duration of contraception required for women of childbearing potential. We included 17 studies for analysis in our systematic review. A total of 595 women were treated with immunochemotherapy during pregnancy, with a median age of 29 years (range 14-48). Of these, 81 women (14%) were treated in the first trimester, and 514 (86%) were treated in the second and third trimesters collectively. In total, 68 trials for acute myeloid leukaemia, acute lymphocytic leukaemia, high-grade non-Hodgkin lymphoma, and Hodgkin lymphoma (40%, 26%, 21%, and 13%, respectively) were included in our ClinicalTrials.gov analysis. Most protocols (66 [97%]) explicitly excluded pregnant women, with 40 (69%) not providing a rationale for exclusion. The potential harm to the fetus from anti-cancer therapy has historically been given greater moral precedence than a pregnant woman's autonomy. This pattern is reflected in the lack of rigorous evidence for immunochemotherapy in pregnancy and a universal exclusion of pregnant and lactating women from clinical trial protocols in this study. Nonetheless, the administration of systemic chemotherapy in the second and third trimesters was not associated with an increased rate of congenital malformations or perinatal mortality in our systematic review cohort, with maternal outcomes broadly comparable to those of the non-pregnant population.

Rates of Menstrual History-Taking and Counseling With Anticancer Treatments Are Low: People Who Menstruate Deserve Gender-Specific Cancer Care.

BACKGROUND: Chemotherapy predisposes people who menstruate to abnormal uterine bleeding that can be life-threatening and may also damage ovaries, resulting in premature menopause. The purpose of this study was to explore the incidence of menstrual history documentation and counseling before, during, and after cancer treatment. PATIENTS AND METHODS: The medical charts of 137 consecutive females (self-reported) aged 18 to 49 years receiving anticancer treatment at a major tertiary metropolitan hospital in Australia between 2017 and 2020 were reviewed. Data collected included primary diagnosis, stage of cancer, treatment(s) received, rates of remission or progression, documentation of involvement of a specialist gynecologist, reproductive history, menstrual disturbances, menstruation counseling or intervention offered, and diagnosis of early ovarian failure. RESULTS: Only 16.1% of patients had their menstrual history documented at the initial consult, and 49.6% had their menstrual history documented at a subsequent consult with their treating oncologist or hematologist. Most (82.4%) patients with a menstrual history documented experienced menstrual disturbance posttreatment, most commonly amenorrhea (48.0%), followed by menopause or menopause symptoms (20.6%), irregular menstrual bleeding (16.7%), menorrhagia (13.7%), dysmenorrhea (3.9%), and iron deficiency from bleeding (2.9%). Menopause/Menopausal symptoms and iron deficiency were more likely to be treated than other disturbances. CONCLUSIONS: Menstruation disturbance is a common side effect of cancer treatment. Menstrual care should be integral to cancer care for people who menstruate, and higher engagement could be achieved through education of medical and allied health staff, information technology systems automating prompts and referral pathways, regular audits to ensure compliance, better alliances between cancer and fertility specialists, and the creation of accessible patient information to promote awareness and facilitate discussion.

The clinical features, management and outcomes of lymphoma in pregnancy: A multicentre study by the Australasian Lymphoma Alliance.

Lymphoma in pregnancy (LIP) presents unique clinical, social and ethical challenges; however, the evidence regarding this clinical scenario is limited. We conducted a multicentre retrospective observational study reporting on the features, management, and outcomes of LIP in patients diagnosed between January 2009 and December 2020 at 16 sites in Australia and New Zealand for the first time. We included diagnoses occurring either during pregnancy or within the first 12 months following delivery. A total of 73 patients were included, 41 diagnosed antenatally (AN cohort) and 32 postnatally (PN cohort). The most common diagnoses were Hodgkin lymphoma (HL; 40 patients), diffuse large B-cell lymphoma (DLBCL; 11) and primary mediastinal B-cell lymphoma (PMBCL; six). At a median follow up of 2.37 years, the 2- and 5-year overall survival (OS) for patients with HL were 91% and 82%. For the combined DLBCL and PMBCL group, the 2-year OS was 92%. Standard curative chemotherapy regimens were successfully delivered to 64% of women in the AN cohort; however, counselling regarding future fertility and termination of pregnancy were suboptimal, and a standardised approach to staging lacking. Neonatal outcomes were generally favourable. We present a large multicentre cohort of LIP reflecting contemporary practice and identify areas in need of ongoing research.

The Role of Family Resilience and Pandemic Burnout on Mental Health: A Two-Wave Study in China.

Family resilience refers to the processes through which a family adapts to and bounces back from adversities. Pandemic burnout refers to feeling emotionally exhausted, cynical, and lack of accomplishment during the pandemic and/or toward various preventive polices and measures. This two-wave, region-wide, longitudinal study included 796 adult participants residing in mainland China. Participants completed online surveys at two time points during the COVID-19 pandemic. Time 1 (T1) survey was conducted when the number of new infected cases in China stabilized, while Time 2 (T2) was conducted 5 months later when there was a sudden surge of new infected cases. Results of a hierarchical regression analysis revealed that the interaction and main effects of pandemic burnout and family resilience at T2 showed significant incremental prediction of depression and anxiety at T2, after controlling for demographic as well as individual and family resilience at T1. These results supported the hypotheses that current family resilience functions as a protective factor, whereas pandemic burnout functions as a risk factor of mental health during successive waves of pandemic outbreaks. In particular, family resilience at T2 mitigated the negative impact of high pandemic burnout on anxiety and depression at T2.

Capturing the lived experiences of women with lymphoma in pregnancy: a qualitative study.

Lymphoma in pregnancy is a rare and challenging diagnosis that complicates ∼1:6000 pregnancies; posing a series of unique therapeutic, social, and ethical challenges to the patient, her family, and the medical professionals involved. These difficulties are compounded by the paucity of real-world data on the management of LIP, and a lack of relevant support systems for women in this setting. We conducted a retrospective multicenter qualitative study, interviewing women aged ≥18 years of age diagnosed with Hodgkin (HL) or non-Hodgkin lymphoma (NHL) during pregnancy or within 12 months postpartum, between 1 January 2009 and 31 December 2020 from 13 Australasian sites. Semi-structured telephone interviews were conducted, recorded, and analyzed using QSR Int NVivo 12 Pro (March 2020, USA) to quantify salient themes. Of the 32 women interviewed, 20 (63%) were diagnosed during pregnancy (16, 34, and 13% in the 1st, 2nd, and 3rd trimesters, respectively), while 12 (37%) were diagnosed post-partum. Women recalled that their chief concerns at diagnosis were the welfare of their child (n = 13, 41%) and a fear of dying (n = 9, 28%). Perceived diagnostic delay attributed to pregnancy was reported by 41% of participants. Other key themes were communication, educational materials, psychosocial supports, and oncofertility issues. To our knowledge this is the first report capturing the lived experiences of survivors of lymphoma during pregnancy, affording a unique opportunity to consider the management, psychosocial supports, and delivery of care to meet the needs of these women.What is the NEW aspect of your work? To our knowledge, this is the first report capturing and analyzing the healthcare experiences of survivors of Lymphoma in Pregnancy (LIP).What is the CENTRAL finding of your work? Women valued clear and empathic communication, provision of tailored educational materials, access to psychosocial supports (particularly childcare and financial supports), and timely oncofertility management in their healthcare journey.What is (or could be) the SPECIFIC clinical relevance of your work? Women's personal accounts of positive and negative experiences of LIP care provide insights into their specific concerns and needs which can shape healthcare policy and development of a specific framework for managing and supporting patients with LIP (and other cancers).

Role of EXO1 nuclease activity in genome maintenance, the immune response and tumor suppression in Exo1D173A mice.

DNA damage response pathways rely extensively on nuclease activity to process DNA intermediates. Exonuclease 1 (EXO1) is a pleiotropic evolutionary conserved DNA exonuclease involved in various DNA repair pathways, replication, antibody diversification, and meiosis. But, whether EXO1 facilitates these DNA metabolic processes through its enzymatic or scaffolding functions remains unclear. Here, we dissect the contribution of EXO1 enzymatic versus scaffolding activity by comparing Exo1DA/DA mice expressing a proven nuclease-dead mutant form of EXO1 to entirely EXO1-deficient Exo1-/- and EXO1 wild type Exo1+/+ mice. We show that Exo1DA/DA and Exo1-/- mice are compromised in canonical DNA repair processing, suggesting that the EXO1 enzymatic role is important for error-free DNA mismatch and double-strand break repair pathways. However, in non-canonical repair pathways, EXO1 appears to have a more nuanced function. Next-generation sequencing of heavy chain V region in B cells showed the mutation spectra of Exo1DA/DA mice to be intermediate between Exo1+/+ and Exo1-/- mice, suggesting that both catalytic and scaffolding roles of EXO1 are important for somatic hypermutation. Similarly, while overall class switch recombination in Exo1DA/DA and Exo1-/- mice was comparably defective, switch junction analysis suggests that EXO1 might fulfill an additional scaffolding function downstream of class switching. In contrast to Exo1-/- mice that are infertile, meiosis progressed normally in Exo1DA/DA and Exo1+/+ cohorts, indicating that a structural but not the nuclease function of EXO1 is critical for meiosis. However, both Exo1DA/DA and Exo1-/- mice displayed similar mortality and cancer predisposition profiles. Taken together, these data demonstrate that EXO1 has both scaffolding and enzymatic functions in distinct DNA repair processes and suggest a more composite and intricate role for EXO1 in DNA metabolic processes and disease.

Monoclonal B-cell Lymphocytosis - a review of diagnostic criteria, biology, natural history, and clinical management.

Since first described almost two decades ago, there has been significant evolution in our definition and understanding of the biology and implications of monoclonal B-cell lymphocytosis (MBL). This review provides an overview of the definition, classification, biology, and natural history of MBL, mainly focused on the dominant CLL-like phenotype form of MBL. The increasingly recognized implications of MBL with respect to immune dysfunction are discussed, particularly in view of the COVID-19 pandemic, along with management recommendations for MBL in the clinic.

Family Resilience Scale Short Form (FRS16): Validation in the US and Chinese Samples.

Family resilience, which refers to the processes through which a family adapts to and thrives from adversities, has growing importance in recent years. In response to the need for further research on family resilience, the present research aims to abbreviate and validate Sixbey's Family Resilience Assessment Scale (FRAS) into a 16-item version Family Resilience Scale Short Form in the US (FRS16) and Chinese (FRS16_C) samples. The samples included 1,236 (Study 1) and 1,135 (Study 2) participants from the US and China, respectively. Results of confirmatory factor analysis (CFA) supported the proposed three-factor structure of FRS16: Family Communication and Connectedness, Positive Framing, and External Support across two samples. Overall, the reliability and validity of full and subscales of FRS16 and FRS16_C were satisfactory. Multi-group CFA revealed that both configural and metric invariance are supported, suggesting that participants in the US and Chinese samples assign comparable meaning to the latent factors of FRS16. Results suggested that FRS16 and FRS16_C are valid instruments for family resilience in the US and Chinese samples.

Deep learning model of somatic hypermutation reveals importance of sequence context beyond hotspot targeting.

B cells undergo somatic hypermutation (SHM) of the Immunoglobulin (Ig) variable region to generate high-affinity antibodies. SHM relies on the activity of activation-induced deaminase (AID), which mutates C>U preferentially targeting WRC (W=A/T, R=A/G) hotspots. Downstream mutations at WA Polymerase η hotspots contribute further mutations. Computational models of SHM can describe the probability of mutations essential for vaccine responses. Previous studies using short subsequences (k-mers) failed to explain divergent mutability for the same k-mer. We developed the DeepSHM (Deep learning on SHM) model using k-mers of size 5-21, improving accuracy over previous models. Interpretation of DeepSHM identified an extended WWRCT motif with particularly high mutability. Increased mutability was further associated with lower surrounding G content. Our model also discovered a conserved AGYCTGGGGG (Y=C/T) motif within FW1 of IGHV3 family genes with unusually high T>G substitution rates. Thus, a wider sequence context increases predictive power and identifies features that drive mutational targeting.

Sibling Violence and Psychological Adjustment: The Role of Maladaptive Coping and Maternal Authoritativeness.

This study examined the phenomenon of sibling violence in Singapore. The underlying mechanisms through which maternal authoritativeness and maladaptive coping influenced psychological adjustment following sibling violence were also investigated. Questionnaires were administered to 287 female and 128 male Singaporean college students between the ages of 18 to 27. Results showed that lifetime and past-year prevalence estimates of sibling violence in college students in Singapore were 89.9% and 62.0%, respectively. Lifetime psychological sibling violence involvement and past-year sibling violence involvement (both physical and psychological) were significantly related to maladaptive coping and overall psychological adjustment; lifetime sibling violence involvement was significantly related to maternal authoritativeness, anxiety, and depression only. Maladaptive coping was found to be a significant mediator between past-year physical and psychological sibling violence involvement and two measures of psychological adjustment, anxiety and depression. Maternal authoritativeness functioned as a moderator only for the relationship between past-year psychological sibling violence exposure and psychological adjustment. At low but not high levels of maternal authoritativeness, past-year psychological violence involvement was significantly related to higher levels of anxiety and depression, and lower levels of self-esteem. These findings show that sibling violence is a pervasive problem in Asian countries as well, such as in Singapore. There is a need to educate both the public and the relevant authorities so that steps can be taken to protect those who have experienced or are at risk of experiencing such violence. Through elucidating the role of maternal authoritativeness and maladaptive coping, the present study also suggests new avenues for interventions to reduce the adverse effects of sibling violence. Limitations and future directions are also discussed.

COVID-19 vaccine failure in chronic lymphocytic leukaemia and monoclonal B-lymphocytosis; humoural and cellular immunity.

Chronic lymphocytic leukaemia (CLL) is associated with immunocompromise and high risk of severe COVID-19 disease and mortality. Monoclonal B-cell lymphocytosis (MBL) patients also have immune impairment. We evaluated humoural and cellular immune responses in 181 patients with CLL (160) and MBL (21) to correlate failed seroconversion [<50 AU/ml SARS-CoV-2 II IgG assay, antibody to spike protein; Abbott Diagnostics)] following each of two vaccine doses with clinical and laboratory parameters. Following first and second doses, 79.2% then 45% of CLL, and 50% then 9.5% of MBL patients respectively remained seronegative. There was significant association between post dose two antibody level with pre-vaccination reduced IgM (p < 0.0001), IgG2 (p < 0.035), and IgG3 (p < 0.046), and CLL therapy within 12 months (p < 0.001) in univariate analysis. By multivariate analysis, reduced IgM (p < 0.0002) and active therapy (p < 0.0002) retained significance. Anti-spike protein levels varied widely and were lower in CLL than MBL patients, and both lower than in normal donors. Neutralisation activity showed anti-spike levels <1000 AU/ml were usually negative for both an early viral clade and the contemporary Delta variant and 72.9% of CLL and 53.3% of MBL failed to reach levels ≥1000 AU/ml. In a representative sample, ~80% had normal T-cell responses. Failed seroconversion occurred in 36.6% of treatment-naïve patients, in 78.1% on therapy, and in 85.7% on ibrutinib.