Notes

Pd-Single-Atom Matched up Biocatalysts pertaining to Chem-/Sono-/Photo-Trimodal Growth Remedies.
Magnetic nanomaterials have received great attention in different biomedical applications. Biofunctionalizing these nanomaterials with specific targeting agents is a crucial aspect to enhance their efficacy in diagnostics and treatments while minimizing the side effects. The benefit of magnetic nanomaterials compared to non-magnetic ones is their ability to respond to magnetic fields in a contact-free manner and over large distances. This allows to guide or accumulate them, while they can also be monitored. Recently, magnetic nanowires (NWs) with unique features were developed for biomedical applications. The large magnetic moment of these NWs enables a more efficient remote control of their movement by a magnetic field. This has been utilized with great success in cancer treatment, drug delivery, cell tracing, stem cell differentiation or magnetic resonance imaging. In addition, the NW fabrication by template-assisted electrochemical deposition provides a versatile method with tight control over the NW propebility assay.Early diagnosis of systemic sclerosis-related interstitial lung disease (SSc-ILD) is important to enable treatment to be administered with minimal delay. However, diagnosing SSc-ILD is challenging because key symptoms are non-specific. High-resolution computed tomography (HRCT) of the chest is recognized as a sensitive imaging method for diagnosing and assessing SSc-ILD. Exposure of patients to ionizing radiation may be considered as a limitation, although methodological steps may be taken to moderate this. We present practical recommendations for performing HRCT scans and interpreting the results. Key features of SSc-ILD on HRCT include a non-specific interstitial pneumonia (NSIP) pattern with peripheral ground-glass opacities and extensive traction bronchiectasis. Despite similarities between SSc-ILD and idiopathic pulmonary fibrosis (IPF), HRCT can be used to differentiate between these conditions in SSc-ILD compared with IPF, there is a greater proportion of ground-glass opacity and fibrosis is less coarse. A dilated, air-filled esophagus with diameter >10 mm, suggestive of esophageal dysmotility is commonly seen in SSc-ILD. Pulmonary artery size greater than the adjacent ascending aorta suggests coexistent pulmonary hypertension. Nodules must be monitored due to the increased risk of lung cancer. A large extent of disease on HRCT (≥20%) or a high fibrosis score suggests an increased risk of mortality. HRCT is central to diagnosing SSc-ILD, and serial assessments can be helpful in monitoring disease progression or treatment response.
Serum hepatitis B core-related antigen (HBcrAg) levels reflect intrahepatic HBV replication activity. We aimed to study whether HBcrAg levels predict response to pegylated interferon (PEG-IFN) treatment in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients.

We studied HBcrAg levels in 222 HBeAg-positive patients treated with PEG-IFN with or without lamivudine for 52 weeks in a global randomized trial and compared kinetics across treatment arms and types of response. Optimal HBcrAg cutoffs for stopping therapy were compared to and combined with the currently recommended hepatitis B surface antigen (HBsAg)-based stopping-rules.

Baseline HBcrAg levels could not discriminate between responders and non-responders (P=0.91). HBcrAg levels of patients responding to PEG-IFN therapy showed a more pronounced on-treatment decline (mean declines 3.4 versus 1.0 log U/ml; P<0.0001), which was sustained until the end of follow-up (mean declines week 78, 3.8 versus 1.0 log U/ml; P<0.0001). In the PEG-IFN monotherapy group, HBcrAg levels of >8.35 log U/ml at week 24 identified 19 patients (19%) of whom 1 (negative predicitve value [NPV]=95%) achieved a response. The performance of this HBcrAg-based stopping rule alone was not superior to the one based on HBsAg >20,000 IU/ml. Among patients with an HBsAg <20,000 (n=56), 9 (16%) had an HBcrAg >8.35, of whom 8 achieved no response (NPV 89%).

HBeAg-positive CHB patients with a response to PEG-IFN therapy achieve a more pronounced HBcrAg decline. HBcrAg levels at week 24 of therapy could be used to identify non-responders in combination with the established HBsAg-based stopping-rules.
HBeAg-positive CHB patients with a response to PEG-IFN therapy achieve a more pronounced HBcrAg decline. HBcrAg levels at week 24 of therapy could be used to identify non-responders in combination with the established HBsAg-based stopping-rules.
As the coronavirus disease 2019 (COVID-19) pandemic grows daily, we remain with no prophylactic and only minimal therapeutic interventions to prevent or ameliorate severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Prior to SARS-CoV-2 emergence, high throughput screens utilizing clinically developed drugs identified compounds with in vitro inhibitory effect on human coronaviruses that may have potential for repurposing as treatment options for COVID-19. However, caution should be applied to repurposing of these drugs when they are taken out of context of human pharmacokinetic parameters associated with normal therapeutic use.

Our aim was to provide a tier-based scoring system to interrogate this data set and match each drug with its human pharmacokinetic criteria, such as route of administration, therapeutic plasma levels and half-life, tissue distribution and safety.

Our analysis excluded most previously identified drugs but identified members of four drug classes (antimalarial amino-quinolones, selective estrogen receptor modulators [SERMs], low potency tricyclic antipsychotics and tricyclic antidepressants) as potential drug candidates for COVID-19. Two of them, the tricyclic antipsychotics and tricyclic antidepressants were further excluded based on a high adverse event profile.

In summary, our findings using a new pharmacokinetic-based scoring system supports efficacy testing of only a minority of candidates against SARS-CoV-2 infection.
In summary, our findings using a new pharmacokinetic-based scoring system supports efficacy testing of only a minority of candidates against SARS-CoV-2 infection.
Stillbirths and neonatal deaths have long been imperfectly classified and recorded worldwide. In Hong Kong, the current code system is deficient (>90% cases with unknown causes) in providing the diagnoses of perinatal mortality cases.

The objective of this study was to apply the International Classification of Diseases for Perinatal Mortality (ICD-PM) system to existing perinatal death data. Further, the aim was to assess whether there was any change in the classifications of perinatal deaths compared with the existing classification system and identify any areas in which future interventions can be made.

We applied the ICD-PM (with International Statistical Classification of Diseases and Related Health Problems, 10th Revision) code system to existing perinatal death data in Kwong Wah Hospital, Hong Kong, to improve diagnostic classification. The study included stillbirths (after 24 weeks gestation) and neonatal deaths (from birth to 28 days). The retrospective data (5 years) from May 1, 2012, to Aprse perinatal deaths.
Using the ICD-PM would lead to a better classification of perinatal deaths, reduce the proportion of unknown diagnoses, and clearly link the maternal conditions with these perinatal deaths.
Shared decision making (SDM) is a health communication model that evolved in Europe and North America and largely reflects the values and medical practices dominant in these areas.

This study aims to understand the beliefs, perceptions, and practices related to SDM and patient-centered care (PCC) of physicians in Israel, Jordan, and the United States.

A hypothesis-generating comparative survey study was administered to physicians from Israel, Jordan, and the United States.

A total of 36 surveys were collected via snowball sampling (Jordan n=15; United States n=12; Israel n=9). SDM was perceived as a way to inform patients and allow them to participate in their care. Barriers to implementing SDM varied based on place of origin; physicians in the United States mentioned limited time, physicians in Jordan reported that a lack of patient education limits SDM practices, and physicians in Israel reported lack of communication training. Most US physicians defined PCC as a practice for prioritizing patient prld clarify these differences.
Almost half (46%) of Americans have used a smart assistant of some kind (eg, Apple Siri), and 25% have used a stand-alone smart assistant (eg, Amazon Echo). This positions smart assistants as potentially useful modalities for retrieving health-related information; however, the accuracy of smart assistant responses lacks rigorous evaluation.

This study aimed to evaluate the levels of accuracy, misinformation, and sentiment in smart assistant responses to human papillomavirus (HPV) vaccination-related questions.

We systematically examined responses to questions about the HPV vaccine from the following four most popular smart assistants Apple Siri, Google Assistant, Amazon Alexa, and Microsoft Cortana. One team member posed 10 questions to each smart assistant and recorded all queries and responses. Two raters independently coded all responses (κ=0.85). We then assessed differences among the smart assistants in terms of response accuracy, presence of misinformation, and sentiment regarding the HPV vaccine.ative sentiments. Lipopolysaccharides More collaboration between technology companies and public health entities is necessary to improve the retrieval of accurate health information via smart assistants.
Smart assistants appear to be average-quality sources for HPV vaccination information, with Alexa responding most reliably. Cortana returned the largest proportion of inaccurate responses, the most misinformation, and the greatest proportion of results with negative sentiments. More collaboration between technology companies and public health entities is necessary to improve the retrieval of accurate health information via smart assistants.Akt is a critical protein kinase that governs cancer cell growth and metabolism. Akt appears to be autoinhibited by an intramolecular interaction between its N-terminal pleckstrin homology (PH) domain and kinase domain, which is relieved by C-tail phosphorylation, but the precise molecular mechanisms remain elusive. Here, we use a combination of protein semisynthesis, NMR, and enzymological analysis to characterize structural features of the PH domain in its autoinhibited and activated states. We find that Akt autoinhibition depends on the length/flexibility of the PH-kinase linker. We identify a role for a dynamic short segment in the PH domain that appears to regulate autoinhibition and PDK1-catalyzed phosphorylation of Thr308 in the activation loop. We determine that Akt allosteric inhibitor MK2206 drives distinct PH domain structural changes compared to baseline autoinhibited Akt. These results highlight how the conformational plasticity of Akt governs the delicate control of its catalytic properties.During meiosis, homologous chromosomes pair and recombine, enabling balanced segregation and generating genetic diversity. In many vertebrates, double-strand breaks (DSBs) initiate recombination within hotspots where PRDM9 binds, and deposits H3K4me3 and H3K36me3. However, no protein(s) recognising this unique combination of histone marks have been identified. We identified Zcwpw1, containing H3K4me3 and H3K36me3 recognition domains, as having highly correlated expression with Prdm9. Here, we show that ZCWPW1 has co-evolved with PRDM9 and, in human cells, is strongly and specifically recruited to PRDM9 binding sites, with higher affinity than sites possessing H3K4me3 alone. Surprisingly, ZCWPW1 also recognises CpG dinucleotides. Male Zcwpw1 knockout mice show completely normal DSB positioning, but persistent DMC1 foci, severe DSB repair and synapsis defects, and downstream sterility. Our findings suggest ZCWPW1 recognition of PRDM9-bound sites at DSB hotspots is critical for synapsis, and hence fertility.
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