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BackgroundPoor treatment outcomes among people with drug-resistant TB (DR-TB) are a major concern. Heteroresistance (presence of susceptible and resistant Mycobacterium tuberculosis in the same sample) has been identified in some people with TB, but its impact on treatment outcomes is unknown.MethodsWe used targeted deep sequencing to identify mutations associated with DR-TB and heteroresistance in culture samples of 624 people with DR-TB. We evaluated the association between heteroresistance and time to unfavorable treatment outcome using Cox proportional hazards regression.ResultsThe proportion of drug-resistant isolates with a known mutation conferring resistance was lower for streptomycin (45.2%) and second-line injectables (79.1%) than for fluoroquinolones (86.7%), isoniazid (93.2%) and rifampin (96.5%). Fifty-two (8.3%) had heteroresistance, and it was more common for fluoroquinolones (4.6%) than rifampin (2.2%), second-line injectables (1.4%), streptomycin (1.7%), or isoniazid (1.3%). There was no association between heteroresistance and time to unfavorable outcome among people with multidrug-resistant TB (adjusted hazard ratio [aHR] 1.74, 95% CI 0.39-7.72) or pre-extensively DR-TB (aHR 0.65, 95% CI 0.24-1.72).ConclusionsHeteroresistance was relatively common (8.3%) among people with DR-TB in the Philippines. However, we found insufficient evidence to demonstrate an impact on unfavorable treatment outcomes.

Background: The combination of atezolizumab with etoposide and carboplatin (AECb) has become a new standard of care for extensive-stage small-cell lung cancer (ES-SCLC). This study evaluates its impact on central nervous system (CNS) progression, specifically brain metastases., Method: We analyzed the outcomes of 550 ES-SCLC patients who received first-line therapy between 2016 and 2022, focusing on time to intracranial progression (TTicP), progression-free survival (PFS), and overall survival (OS)., Results: Of the 550 patients, 247 (44.9 %) received AECb, while 303 (55.1 %) received conventional chemotherapy (CTx). Intracranial progression occurred in 179 patients (32.5 %), with the AECb group showing a significantly prolonged TTicP compared to the CTx group (median 24.4 vs. 14.3 months; p = 0.038). In patients without brain metastasis at diagnosis (n = 408), TTicP was also longer in the AECb group (27.2 vs. 15.3 months; p = 0.016). This benefit persisted even after excluding patients who underwent prophylactic cranial irradiation (PCI) (27.2 vs. 15.2 months; p = 0.02) (n = 394). These findings remained consistent after adjusting for age, initial metastatic site, and PCI. Additionally, the AECb group showed improved PFS (5.0 vs. 4.7 months; p = 0.004) and OS (11.1 vs. 9.8 months; p = 0.003)., Conclusion: Our findings suggest that the AECb regimen is superior to conventional chemotherapy in delaying CNS progression and controlling systemic disease in ES-SCLC. These results support the AECb regimen as the new standard of care. Further research is needed to explore the mechanisms behind these improved CNS outcomes and to reassess the necessity of PCI in this treatment era., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)

Background: The prognosis for patients with lung cancer bone metastases has improved with the use of novel systemic agents. These patients might need surgery or radiotherapy to alleviate symptoms or maintain function. However, there is currently no disease specific algorithm to guide multidisciplinary decisions. Methods : The inclusion criteria encompassed studies with ≥10 patients offering multivariate analysis data on survival that were published after 2000 until September 2023. Clinical factors were categorized based on their characteristics and the pooled hazard ratios (HRs) for each category were calculated. A treatment algorithm was proposed based on clinical importance and the pooled HRs. Results : Fifteen studies involving 3759 patients with lung cancer bone metastases were included. The median survival ranged between 1.8-28.3 months (median: 12.4). Among the studies involving patients with EGFR+ or treated with TKIs, the median survival ranged between 19.5-28.3 months. The most reported significant factor was ECOG performance (nine studies) followed by chemotherapy use (six studies). In the pooled analyses, the pooled HR [95% confidence interval (CI)] of the EGFR status category was 2.109 (1.345-3.305); the ECOG performance category was 2.007 (1.536-2.622); the visceral metastases category was 2.060 (1.370-3.098); the bone metastases characteristics category (e.g., multiplicity, weight-bearing bone metastases) was 1.910 (1.443-2.527); the body weight category was 1.805 (1.334-2.442); the anti-absorbants category was 1.784 (1.448-2.196); the systemic treatment category was 1.695 (1.407-2.041); the skeletal-related event category was 1.616 (1.063-2.458); the smoking status category was 1.530 (1.306-1.793); the gender category was 1.482 (1.270-1.729); and the histology category was 1.450 (1.186-1.772). Conclusions : Oncological prognoses are influenced by various interrelated factors. Our treatment algorithm supports multidisciplinary strategies for managing NSCLC bone metastases, considering the complex factors influencing prognosis.

Various aspects of the new development of organic-inorganic hybrid [N(CH 3 ) 4 ] 2 MnCl 4 single crystals have been discussed. The phase transition temperatures were determined to be 268 K (T C2 ) and 291 K (T C1 ), and the thermodynamic stability was maintained at temperatures up to 669 K. The crystal structures at 250 K (phase III), 275 K (phase II), and 300 K (phase I) are monoclinic, orthorhombic, and orthorhombic, respectively. Notably, while the  1 H and  13 C chemical shifts gradually changed near T C1 and T C2 , the  14 N resonance frequency exhibited a split in the number of signals near T C1 . Furthermore, the shorter spin-lattice relaxation time T 1ρ of  1 H than that of  13 C suggests facile energy transfer for 1 H. Additionally, analysing the temperature dependencies of T 1ρ for  13 C revealed that the activation energy E a in phase I is approximately five times greater than those in phases III and II. The high E a observed in phase I primarily stems from the collective motion of the N(CH 3 ) 4 group, which contrasts with the considerable freedom observed for the CH 3 group in phases III and II. These distinctive physical properties suggest potential applications for [N(CH 3 ) 4 ] 2 MnCl 4 as an organic‒inorganic hybrid material., (© 2024. The Author(s).)

Organic-inorganic hybrid single crystals of (CH 3 NH 3 ) 2 ZnBr 4 were grown by the aqueous solution technique, and their structure, phase transition temperature, and thermal stability were discussed. The crystals were determined to have a monoclinic structure using X-ray diffraction on single crystals, and a transition temperature of 458 K was confirmed from the differential scanning calorimetry and X-ray diffraction analyses on powders. Moreover, the compound exhibited excellent thermal stabilities up to 550 K. The 1 H and 13 C nuclear magnetic resonance chemical shifts of CH 3 shifted in the positive direction as the temperature increased, while the 1 H chemical shift of NH 2 exhibited minor variations in N-H···Br hydrogen bonding, which was influenced by minor changes in the bromide ions surrounding Zn in the ZnBr 4 anion. The spin-lattice relaxation time, which indicates the energy transfer near 1 H and 13 C, exhibited similar values, which is because 1 H and 13 C are bonded to each other in the CH 3 NH 3 cation. This compound exhibits high structural and thermal stabilities and is expected to pave the way for future applications., Competing Interests: The author declares no competing financial interest., (© 2024 The Author. Published by American Chemical Society.)

As part of obtaining excellent properties that can be used as lead-free hybrid solar cells, the crystal growth, crystal structure, phase transition temperature, and thermal properties for [NH 3 (CH 2 ) 2 NH 3 ]CuBr 4 were discussed. The crystal structure at 300 K was determined to be monoclinic by single-crystal X-ray diffraction (XRD) analysis. The phase transition temperatures were determined to be 447 and 473 K, and the results were consistent with the powder XRD patterns. Thermogravimetric analysis revealed thermal stability up to ~ 460 K. The continuous changes in the 1 H and 13 C chemical shifts and 14 N static resonance frequency with increasing temperature are related to variations in the local environment and coordination geometry. The significant differences in activation energies obtained from the 1 H and 13 C spin-lattice relaxation times (t 1ρ ) at low and high temperatures were discussed. The activation energy results suggested that the energy barrier at low temperatures was related to the reorientation of the NH 3 and CH 2 groups around the three-fold symmetry axis, and the energy barrier at high temperatures was related to the reorientation of the [NH 3 (CH 2 ) 2 NH 3 ] cation. These physical properties will be provide important insights or potential applications of this crystal.Please check and confirm that the corresponding author and their respective corresponding affiliation have been correctly identified and amend if necessary.OK !, (© 2024. The Author(s).)

The crystal structure of NH 2 (CH 3 ) 2 CuCl 3 , an organic-inorganic hybrid perovskite, undergoes a phase transition from triclinic to monoclinic at the phase transition temperature T C of 287 K. We investigated the temperature dependencies of NMR chemical shifts and spin-lattice relaxation time T 1ρ to gain insights into the structural geometry and molecular dynamics during the transition from phase II to phase I at high temperatures. Analysis of the 1 H and 13 C NMR chemical shifts of the cation revealed a continuous change in the surrounding structural geometry with temperature, without any anomalous changes around T C . The sudden decrease in T 1ρ values from low to high temperatures indicated a significant variation in proton and carbon dynamics at T C , arising from the slowing motion of molecular dynamics across the phase transition. The activation energies E a obtained from the temperature dependence of T 1ρ for 1 H and 13 C were larger in phase I than in phase II. This suggests that molecular motions in phase II exhibit a higher degree of freedom compared to those in phase I, where they are more constrained. These findings on NH 2 (CH 3 ) 2 CuCl 3 are presented to enhance its potential applications by elucidating the crystal configuration and structural molecular dynamics of ABX 3 type compound., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: This phase Ib study was performed to determine the safety of combination capecitabine with alpleisib (phosphatidylinositol 3-kinase catalytic subunit p110α blockade) and determine the maximal tolerated dose (MTD) and recommended phase ll dose (RP2D) of this combination regimen in patients with advanced solid tumors refractory to standard therapy. The synergistic anti-tumor activity and pharmacokinetics (PK) were investigated., Methods: Dose escalation phases were conducted in patients with advanced solid cancers who were refractory to standard therapy regardless of PIK3CA mutation. Patients were administered orally once daily alpelisib (200mg and 300mg) and twice daily capecitabine (850mg, 1000mg, 1250mg orally, days 1-14) every 3 weeks. Standard "3 + 3" dose escalation was used to define the MTD. The effect of alpelisib on the PK of capecitabine was assessed., Results: Patients with 6 colorectal cancer (three PIK3CA mutation) and 6 breast cancer (all PIK3CA mutation) were enrolled. The first three patients in dose level 0 (alpelisib 200mg daily, capecitabine 1,000 mg/m 2 twice daily) had no dose-limiting toxicities (DLTs). In dose level 1 (alpelisib increased to 300 mg daily, capecitabine 1,000mg twice daily), one of six patients had DLT (grade (Gr) 3 hyperglycemia). When dose level 2 (alpelisib 300mg daily, capecitabine 1,250 mg/m 2 twice daily) was expanded to 3 patients, no patients had DLTs. The combination of alpelisib 300mg daily and capecitabine 1,250 mg/m 2 twice daily was declared as the MTD/RP2D in patients with advanced solid tumors. The most common AEs were Gr 1-3 hyperglycemia (75.0%). Frequent all-grade, treatment-related AEs included Gr 2-3 nausea (75.0%), Gr 1-2 diarrhea (50.0%), Gr 1-2 hand-foot syndrome (41.7%), Gr 1-2 anorexia (41.7%), Gr 2 mucositis (33.3%). Antitumor activity was observed in patients with PIK3CA mutant breast cancer (3 partial response and 3 stable disease of total 6 patients). Alpelisib exposure (C max and AUC 0-12 ) was unaffected by concomitant capecitabine. There were no clinically relevant drug-drug interactions observed between alpelisib and capecitabine., Conclusions: The combination of alpelisib and capecitabine is generally tolerated, without pharmacokinetic interactions, and shows antitumor activity in patients with PIK3CA mutant advanced cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lim, Kim, Kim, Hyun, Park, Kim and Lee.)

Understanding the physical properties of the organic-inorganic hybrid NH(CH 3 ) 3 CuCl 3 ·2H 2 O is necessary for its potential applications. Initially, the monoclinic structure of this crystal was discussed via single-crystal X-ray diffraction. Moreover, the previously unknown phase transition temperature was 350 K, as revealed by differential scanning calorimetry and powder X-ray diffraction. Attributed to ferroelasticity, domain walls were observed between the temperatures T c (Low) (223 K) and T c (High) (350 K). Furthermore, changes in chemical shifts for 1 H and 13 C indicated alterations in the molecular environment, whereas a notable decrease in line width was attributed to increased molecular motion freedom. Subsequently, spin-lattice relaxation times ( T 1ρ values) for 1 H and 13 C (indicative of energy transfer) were influenced by tumbling motions. The high activation energy barrier for molecular reorientation was associated with the tumbling motion of methyl groups around the triple symmetry axis. These foundational properties guide the development of efficient organic-inorganic hybrids suitable for practical applications., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The organic-inorganic hybrid perovskite compounds have been extensively studied since the dawn of a new era in the field of photovoltaic applications. Up to now, perovskites have proven to be the most promising in terms of power conversion efficiency; however, their main disadvantages for use in solar cells are toxicity and chemical instability. Therefore, it is essential to develop a hybrid perovskite that can be replaced with lead-free materials. This review focuses on the possibility of applying lead-free organic-inorganic perovskite types [NH 3 (CH 2 ) n NH 3 ]MCl 4 (n = 2, 3, 4, 5, and 6; M = Mn, Co, Cu, Zn, and Cd) crystals. We are seeking organic-inorganic hybrid perovskite materials with very high temperature stability or without phase transition temperature, and thermal stability. Thus, by considering the characteristics according to the methylene lengths and the various transition metals, we aim to identify improved materials meeting the criteria mentioned above. Consequently, the physicochemical properties of organic-inorganic hybrid perovskite [NH 3 (CH 2 ) n NH 3 ]MCl 4 regarding the effects of various transition metal ions of the anion and the methylene lengths of the cation are expected to promote the development and application of lead-free hybrid perovskite solar cells., (© 2024. The Author(s).)

The NMR chemical shifts, linewidths, spin-lattice relaxation times in the rotating system T 1ρ , and spin-lattice relaxation times in the laboratory system T 1 were evaluated for the perovskite-type N(CH 3 ) 4 CdBr 3 crystal, aiming to understand the changes in the structural geometry and molecular dynamics from phase I to phase II. From the temperature-dependence of the 1 H, 13 C, 14 N, and 113 Cd NMR chemical shifts, the structural geometry underwent a continuous change, without anomalous changes around ( T C = 390 K). However, the linewidths in phase I were narrower than those in phase II, indicating that the motional averaging effects were caused by the rapid rotation of the N(CH 3 ) 4 group. Sudden changes in T 1 and T 1ρ were observed near T C , for which the activation energy E a in phase I was approximately 12 times larger than that in phase II; the small E a values in phase II indicate a large degree of freedom for the methyl group and CdBr 6 octahedra, whereas the large E a in phase I was primarily attributed to the overall N(CH 3 ) 4 and the 113 Cd in the CdBr 6 groups. Consequently, the phase transition mechanisms of N(CH 3 ) 4 CdBr 3 are related to reorientation of the N(CH 3 ) 4 group and the arrangement of the CdBr 6 groups., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Purpose: Chemotherapy-induced nausea and vomiting (CINV) is a common adverse events in cancer patients and can negatively affect their quality of life (QoL). This study aimed to evaluate the clinical efficacy of an electric massage chair (EMC) for the treatment of CINV., Methods: A randomized phase II cross-over trial was conducted on solid cancer patients who received moderate (MEC) to high emetogenic chemotherapy (HEC). The participants were randomly assigned to receive their first chemotherapy either on a standard bed (Group A) or in an EMC (Group B) during the infusion. The patients were then crossed over to the next cycle. CINV and QoL questionnaires were collected from the participants., Results: A total of 59 patients completed the trial protocol and were included in the analysis, with 29 and 30 patients in Groups A and B, respectively. The mean INVR (Index of Nausea, Vomiting, and Retching) score in the 2nd day of the first cycle was higher in Group B (3.63 ± 5.35) than Group A (2.76 ± 4.78), but the difference was not statistically significant (p = 0.5367). The complete response rate showed little difference between the groups. Among the high-emetic risk subgroups, patients who received HEC (p = 0.04595), younger patients (p = 0.0108), and non-colorectal cancer patients (p = 0.0495) presented significantly lower CINV scores when EMC was applied., Conclusion: Overall, there was no significant difference in INVR scores between standard care and EMC. Applying EMC at the first chemotherapy infusion may help preserve QoL and reduce CINV in high-risk patients., Trial Registration: KCT0008200, 17/02/2023, Retrospectively registered., (© 2024. The Author(s).)

Background: Bone-modifying agents (BMA) are key components in the management of cancer patients with bone metastasis. Despite their clinical benefits, the use of BMA is associated with dental adverse events (AEs) including medication-related osteonecrosis of the jaw (MRONJ). This study investigated the frequency of dental surveillance before BMA treatment and the prevalence of dental AEs including MRONJ, after BMA treatment in patients with bone metastasis from breast and prostate cancer using data from the national health insurance system., Methods: Data, including age, cancer diagnosis, administered BMA, and dental AEs during cancer treatment, of patients with bone metastasis from breast and prostate cancer who received at least one infusion of BMA between 2007 and 2019 were extracted from the Korean National Health Insurance Service (KNHIS) dataset., Results: Of the 15,357 patients who received BMA, 1,706 patients (11.1%) underwent dental check-ups before BMA treatment. The proportion of patients receiving dental check-up increased from 4.4% in 2007 to 16.7% in 2019. Referral to dentists for a dental check-up was more active in clinics/primary hospitals than general/tertiary hospitals, and medical doctors and urologists actively consulted to dentists than general surgeons, regardless of the patient's health insurance status. After BMA treatment, 508 patients (3.8%) developed dental AEs, including abscess (42.9%), acute periodontitis (29.7%), acute pericoronitis (14.9%), and MRONJ (12.5% of dental AEs cases, 0.5% of total BMA treated patients)., Conclusions: Considering the long treatment period in patients with metastatic cancer, coordination between dentists and oncologists is necessary to ensure appropriate dental management before the initiation of BMA., (© 2024. The Author(s).)

Understanding the physical properties of organic-inorganic hybrid [NH(CH 3 ) 3 ] 2 ZnCl 4 is necessary for its potential application in batteries and fuel cells due to its environmentally-friendly, and highly stable character. Here, we determine its overall properties in detail, such as its orthorhombic crystal structure, and phase transition temperatures associated with five different phases. Structural geometry was studied by the chemical shifts caused by the local field around 1 H. No changes were observed for the environment around 1 H for CH 3 , whereas the 1 H chemical shifts around NH in the cation were shown due to the change in the hydrogen bond N‒H···Cl. This is related to the change in Cl around Zn in the anion. In addition, the coordination geometry of 14 N and 1 H around 13 C exhibited increased symmetry at high temperatures. Finally, we were able to understand its molecular dynamics by the significant change with temperature observed from the spin-lattice relaxation time T 1ρ values, which represent the energy transfer for the 1 H and 13 C atoms of the cation. The activation energies obtained from the T 1ρ results were 3-4 times large at phase I (> 348 K) than at phase V and IV (< 286 K). The relaxations show that the energy barriers in phases IV and V are related to the reorientation of methyl groups around the triple symmetry axis, while the reorientation of methyl groups of the cation in phase I is related to as a whole., (© 2024. The Author(s).)

Understanding the physical properties of the organic-inorganic hybrid [NH 2 (CH 3 ) 2 ] 2 CuBr 4 is essential to expand its applications. The single [NH 2 (CH 3 ) 2 ] 2 CuBr 4 crystals were grown and their comprehensive properties were investigated. The crystals had a monoclinic structure with the space group P2 1 /n and lattice constants of a = 8.8651 (5) Å, b = 11.9938 (6) Å, c = 13.3559 (7) Å, and β = 91.322°. The transition temperature from phase I to phase II was determined to be 388 K. Variations in the 1 H nuclear magnetic resonance chemical shifts of NH 2 and 14 N NMR chemical shifts according to the temperature changes in the cation were attributed to vibrations of NH 2 groups at their localization sites. The 1 H and 13 C spin-lattice relaxation times (T 1ρ ) in phase II changed significantly with temperature, indicating that these values are governed by molecular motion. The T 1ρ values were much longer in phase I than in phase II, which means energy transfer was difficult. Finally, the activation energies for phases I and II were considered. According to the basic mechanism of [NH 2 (CH 3 ) 2 ] 2 CuBr 4 crystals, organic-inorganic materials may have potential applications in various fields., (© 2023. The Author(s).)

Oligometastasis is defined as the presence of several limited metastatic lesions and is generally limited to three or fewer than five metastatic lesions. Previously, the treatment of metastatic cancer aimed to alleviate symptoms rather than cure them; however, the use of immunotherapy or targeted therapy has greatly improved patient life expectancy. Additionally, the effectiveness and safety of local treatment have recently been proven for oligometastatic cancers and have significantly improved patient survival and decreased recurrence rates. A few metastatic studies on lung cancer have demonstrated the usefulness of combining radiation therapy and immunotherapy. Recently, local and targeted therapy combinations have shown promising results in treating non-small cell lung cancer, predominantly caused by the epidermal growth factor receptor and anaplastic lymphoma kinase gene mutations, suggesting the potential of these new treatment strategies. It is well known that oligometastasis has better clinical results than polymetastasis; however, research on the biological profile of oligometastasis is still lacking. Studies using circulating tumor DNA and circulating tumor cells are at the initial stages of providing a better understanding of oligometastatic cancers, and the biological characteristics of these cancers may be revealed based on more diverse studies. With the development of these treatments, the prognosis for patients with oligometastatic cancers is steadily improving, and if the biological profile is revealed, customized treatment may be provided.

Organic-inorganic hybrid compounds have recently gained significant attention in recent years due to their diverse applications. Herein, [NH 3 (CH 2 ) 6 NH 3 ]ZnCl 4 crystals were grown, and their triclinic structure, phase transition temperature ( T C = 408 K), and high thermal stability ( T d = 584 K) was determined using X-ray diffraction (XRD), differential scanning calorimetry, and thermogravimetry measurements. By analyzing the chemical in response to temperature changes, we observed that the coordination geometry around 1 H and 13 C were highly symmetric below T C , whereas their symmetry was lowered above T C . The change of N-H⋯Cl hydrogen bond from XRD results and the change of 14 N NMR chemical shifts was due to the changes to the coordination geometry of Cl - around Zn 2+ in the ZnCl 4 anion. The activation energy of 1 H was three times greater than that of 13 C, and this result indicates that the energy transfer of 13 C was easier than those of 1 H. We compared the results for [NH 3 (CH 2 ) n NH 3 ]ZnCl 4 ( n = 6) studied here with those for n = 2, 3, 4, and 5 obtained from previous studies. The characteristics of the length of CH 2 in the methylene chain are expected to be used for potential applications in the near future., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A comprehensive understanding of the physicochemical properties of organic-inorganic hybrids is essential for their solid-state lighting applications. Therefore, a single crystal of [NH 2 (CH 3 ) 2 ] 2 CdBr 4 was grown; the crystal structure was monoclinic, and the phase transition temperatures for the four phases IV, III, II, and I were 383 K ( T C1 ), 417 K ( T C2 ), and 427 K ( T C3 ). Furthermore, the chemical shifts caused by the local field around 1 H, 13 C, 14 N, and 113 Cd changed continuously with temperature, especially near T C1 , indicating that the local environment changes with temperature. Owing to the large change in 113 Cd chemical shifts, the coordination geometry of Br around Cd in the CdBr 4 tetrahedra changes near T C1 . Therefore, it is proposed that Br plays a significant role in the N-H···Br hydrogen bond. Finally, the spin-lattice relaxation time T 1ρ , representing the energy transfer around the 1 H and 13 C atoms of the cation, changed significantly with temperature. The activation energies obtained from the T 1ρ results were two times larger at high temperatures than at low temperatures. This study provides an understanding of the fundamental properties of organic-inorganic hybrid compounds to broaden their applications., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Understanding the physicochemical properties of organic-inorganic hybrid materials is essential to promote their applications. In this study, a single crystal of NH 2 (CH 3 ) 2 CdCl 3 was grown, and it exhibited a monoclinic structure. Its phase transition temperatures were 460 and 470 K, and it showed sufficient thermal stability. The changes in the NMR chemical shifts of each atom in the crystal with increasing temperature were determined; the chemical shift of 1 H of NH 2 in the NH 2 (CH 3 ) 2 cation changed with temperature, which was correlated to the changes in the chemical shift of 14 N in NH 2 . The change in 113 Cd chemical shifts indicate the change of six Cl atoms around Cd in CdCl 6 . Therefore, the change in the coordination geometry of CdCl 6 is attributed to the change in the N-H⋯Cl hydrogen bond between the NH 2 (CH 3 ) 2 cation and CdCl 6 anion. In addition, the 13 C activation energies E a obtained from the spin-lattice relaxation time T 1ρ values are smaller than those of the 1 H E a values, suggesting that is free compared to 1 H in the cation. We believe that this study furthers our fundamental understanding of organic-inorganic hybrid materials to promote their practical solar cell applications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals., (© 2023. The Author(s).)

Using DNA methylation profiles ( n = 15,456) from 348 mammalian species, we constructed phyloepigenetic trees that bear marked similarities to traditional phylogenetic ones. Using unsupervised clustering across all samples, we identified 55 distinct cytosine modules, of which 30 are related to traits such as maximum life span, adult weight, age, sex, and human mortality risk. Maximum life span is associated with methylation levels in HOXL subclass homeobox genes and developmental processes and is potentially regulated by pluripotency transcription factors. The methylation state of some modules responds to perturbations such as caloric restriction, ablation of growth hormone receptors, consumption of high-fat diets, and expression of Yamanaka factors. This study reveals an intertwined evolution of the genome and epigenome that mediates the biological characteristics and traits of different mammalian species.

Understanding the physical and chemical properties of the organic-inorganic hybrid NH(CH 3 ) 3 CdCl 3 is essential for its application. Considering its importance, a single crystal of NH(CH 3 ) 3 CdCl 3 was grown with an orthorhombic structure at 300 K. The phase transition temperatures were determined to be 345 ( T C3 ), 376 ( T C2 ), and 452 K ( T C1 ) (phases IV, III, II, and I, respectively, starting from a low temperature). The partial decomposition temperature was 522 K ( T d ). Furthermore, the NMR chemical shifts of the 1 H, 13 C, and 113 Cd atoms of the cation and anion varied with increasing temperature. Consequently, a significant change in the coordination geometry of Cl around Cd in CdCl 6 and a change in the coordination geometry of H in NH was associated with changes in the N-H⋯Cl hydrogen bond near the phase transition temperature. The 13 C activation energy E a obtained from the spin-lattice relaxation time was smaller than that of 1 H E a , suggesting that energy transfer around 13 C is easier. Additionally, a comparison of the twin domain walls measured via optical polarizing microscopy and Sapriel's theory indicated that the crystal structure in phase III was more likely to be orthorhombic than hexagonal., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

An in-depth understanding of the physicochemical properties of the organic-inorganic hybrid [NH 3 (CH 2 ) 2 NH 3 ] 2 CdBr 6 whose structure corresponds to the formulation [NH 3 (CH 2 ) 2 NH 3 ] 2 CdBr 4 · 2Br is essential for its application in batteries, supercapacitors, and fuel cells. Therefore, this study aimed to determine the crystal structure, phase transition, structural geometry, and molecular dynamics of these complexes. Considering its importance, a single crystal of [NH 3 (CH 2 ) 2 NH 3 ] 2 CdBr 6 was grown; the crystal structure was found to be monoclinic. The phase transition temperatures were determined to be 443, 487, 517, and 529 K, and the crystal was thermally stable up to 580 K. Furthermore, the 1 H, 13 C, 14 N, and 113 Cd NMR chemical shifts caused by the local field surrounding the resonating nucleus of the cation and anion varied with increasing temperature, along with the surrounding environments of their atoms. In addition, 1 H spin-lattice relaxation time T 1ρ and 13 C T 1ρ , which represent the energy transfer around the 1 H and 13 C atoms of the cation, respectively, varied significantly with temperature. Consequently, changes in the coordination geometry of Br around Cd in the CdBr 6 anion and the coordination environment around N (in the cation) were associated with changes in the N-H···Br hydrogen bond. The structural geometry revealed critical information regarding their basic mechanism of organic-inorganic hybrid compounds., (© 2023. The Author(s).)

Purpose: Mutations in the PIK3CA gene occur frequently in breast cancer patients. Activating PIK3CA mutations confer resistance to human epidermal growth factor receptor 2 (HER2)-targeted treatments. In this study, we investigated whether PIK3CA mutations were correlated with treatment response or duration in patients with HER2-positive (HER2+) breast cancer., Materials and Methods: We retrospectively reviewed the clinical information of patients with HER2+ breast cancer who received HER2-targeted therapy for early-stage or metastatic cancers. The pathologic complete response (pCR), progression-free survival (PFS), and overall survival were compared between patients with wild-type PIK3CA (PIK3CAw) and those with mutated PIK3CA (PIK3CAm). Next-generation sequencing was combined with examination of PFS associated with anti-HER2 monoclonal antibody (mAb) treatment., Results: Data from 90 patients with HER2+ breast cancer were analyzed. Overall, 34 (37.8%) patients had pathogenic PIK3CA mutations. The pCR rate of the PIK3CAm group was lower than that of the PIK3CAw group among patients who received neoadjuvant chemotherapy for early-stage cancer. In the metastatic setting, the PIK3CAm group showed a significantly shorter mean PFS (mPFS) with first-line anti-HER2 mAb. The mPFS of second-line T-DM1 was lower in the PIK3CAm group than that in the PIK3CAw group. Sequencing revealed differences in the mutational landscape between PIK3CAm and PIK3CAw tumors., Conclusion: Patients with HER2+ breast cancer with activating PIK3CA mutations had lower pCR rates and shorter PFS with palliative HER2-targeted therapy than those with wild-type PIK3CA. Precise targeted-therapy is needed to improve survival of patients with HER2+/PIK3CAm breast cancer.

Background: Although various coronavirus disease 2019 (COVID-19) vaccines have been delivered to the public worldwide, data on cancer populations are limited. Vaccine hesitancy related to safety concerns is observed among cancer patients. We report the perception of COVID-19 vaccines and their safety profile after vaccination among cancer patients., Materials and Methods: Between April and November 2021, a multicenter survey was conducted on 318 patients treated in any hemato-oncology outpatient clinic among three hospitals under the Korea University Medical Center. The medical records of the patients were reviewed to obtain detailed clinical and hematological toxicity data., Results: A perception survey was conducted among 293 patients. Among them, 53.9% were concerned about developing vaccine-related adverse events (VRAEs) and 23.5%, about negative effects on cancer treatment. During the study period, 255 and 186 patients participated in a safety survey after the first and second doses, respectively. After the first dose, 62% of patients reported VRAEs (2.4%, grade 3), whereas 48.9% reported VRAEs (2.7%, grade 3) after the second dose. For both doses, injection-site pain and sore arm pain were the most common VRAEs, followed by myalgia, fatigue, and headache. No grade 4/5 VRAEs were observed, and there were no differences in complete blood count after vaccination. Multivariate analysis revealed female sex, active cancer treatment, and mRNA vaccines as independent risk factors for VRAE development in cancer patients., Conclusion: Despite high levels of concern, COVID-19 vaccines were well tolerated by cancer patients, with a safety profile consistent with that of the general population., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Organic-inorganic hybrid [NH 2 (CH 3 ) 2 ] 2 ZnBr 4 crystals were grown via slow evaporation, and their monoclinic structure was determined using single-crystal X-ray diffraction (XRD). The two phase transition temperatures at 401 K ( T C1 ) and 436 K ( T C2 ) were defined using differential scanning calorimetry and powder XRD. In the nuclear magnetic resonance spectra, a small change was observed in the 1 H chemical shifts for NH 2 , 13 C chemical shifts for CH 3 , and 14 N resonance frequency for NH 2 near T C1 . 1 H spin-lattice relaxation times T 1ρ and 13 C T 1ρ for NH 2 and CH 3 , respectively, rapidly decreased near T C1 , suggesting that energy was easily transferred. NH 2 in the [NH 2 (CH 3 ) 2 ] + cation was significantly influenced by the surrounding environments of 1 H and 14 N, indicating a change in the N-H⋯Br hydrogen bond with the coordination geometry of the ZnBr 4 anion. These fundamental properties open efficient avenues for the development of organic-inorganic hybrids, thus qualifying them for practical applications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Poly(amic acid) (PAA) is prepared by the reaction of dianhydride 4,4'-biphthalic anhydride and diamine bis[4-(3-aminophenoxy)phenyl]sulfone in N,N'-dimethylacetamide. Two types of fillers were dispersed in the as-synthesized PAA via a solution intercalation method; polyimide (PI) hybrid films were synthesized under various heat treatment conditions. Octylamine (C8) was introduced into graphene sheets (C8-GS) and bentonite (C8-BTN), which were then used as nanofillers in the PI hybrid films. The synthesized nanofillers were used in varying amounts of 0.25-1.00 wt% with respect to the matrix PI. The thermal and morphological properties and optical transparency of the hybrid films were investigated and compared for both C8-GS and C8-BTN at varying nanofiller content. The C8-BTN nanocomposite showed superior thermal properties, and optical transparency, and the filler was well dispersed in the PI matrix compared to the C8-GS nanocomposite. The thermal stability of the hybrid films improved upon the addition of small amounts of the nanofiller. However, beyond a certain critical filler concentration, the thermal stability declined. These results were verified through the dispersion of fillers via transmission electron microscopy., (© 2022. The Author(s).)

Introduction: High levels of treatment adherence are critical for achieving optimal treatment outcomes among patients with tuberculosis (TB), especially for drug-resistant TB (DR TB). Current tools for identifying high-risk non-adherence are insufficient. Here, we apply trajectory analysis to characterize adherence behavior early in DR TB treatment and assess whether these patterns predict treatment outcomes., Methods: We conducted a retrospective analysis of Philippines DR TB patients treated between 2013 and 2016. To identify unique patterns of adherence, we performed group-based trajectory modelling on adherence to the first 12 weeks of treatment. We estimated the association of adherence trajectory group with six-month and final treatment outcomes using univariable and multivariable logistic regression. We also estimated and compared the predictive accuracy of adherence trajectory group and a binary adherence threshold for treatment outcomes., Results: Of 596 patients, 302 (50.7%) had multidrug resistant TB, 11 (1.8%) extremely drug-resistant (XDR) TB, and 283 (47.5%) pre-XDR TB. We identified three distinct adherence trajectories during the first 12 weeks of treatment: a high adherence group (n = 483), a moderate adherence group (n = 93) and a low adherence group (n = 20). Similar patterns were identified at 4 and 8 weeks. Being in the 12-week moderate or low adherence group was associated with unfavorable six-month (adjusted OR [aOR] 3.42, 95% CI 1.90-6.12) and final (aOR 2.71, 95% 1.73-4.30) treatment outcomes. Adherence trajectory group performed similarly to a binary threshold classification for the prediction of final treatment outcomes (65.9% vs. 65.4% correctly classified), but was more accurate for prediction of six-month treatment outcomes (79.4% vs. 60.0% correctly classified)., Conclusions: Adherence patterns are strongly predictive of DR TB treatment outcomes. Trajectory-based analyses represent an exciting avenue of research into TB patient adherence behavior seeking to inform interventions which rapidly identify and support patients with high-risk adherence patterns., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Huddart et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Organic-inorganic hybrid [NH 3 (CH 2 ) 6 NH 3 ]ZnBr 4 crystals were prepared by slow evaporation; the crystals had a monoclinic structure with space group P 2 1 / c and lattice constants a = 7.7833 Å, b = 14.5312 Å, c = 13.2396 Å, β = 90.8650°, and Z = 4. They underwent two phase transitions, at 370 K ( T C1 ) and 430 K ( T C2 ), as confirmed by powder X-ray diffraction patterns at various temperatures; the crystals were stable up to 600 K. The nuclear magnetic resonance spectra, obtained using the magic-angle spinning method, demonstrated changes in the 1 H and 13 C chemical shifts were observed near T C1 , indicating changing structural environments around 1 H and 13 C. The spin-lattice relaxation time, T 1ρ , increased rapidly near T C1 suggesting very large energy transfer, as indicated by a large thermal displacement around the 13 C atoms of the cation. However, the environments of 1 H, 14 N, and C1 located close to NH 3 in the [NH 3 (CH 2 ) 6 NH 3 ] cation did not influence it significantly, indicating a minor change in the N-H⋯Br hydrogen bond with the coordination geometry of the ZnBr 4 anion. We believe that the information on the physiochemical properties and thermal stability of [NH 3 (CH 2 ) 6 NH 3 ]ZnBr 4 , as discussed in this study, would be key to exploring its application in stable, environment friendly solar cells., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

In this study, the physicochemical properties of [NH 3 (CH 2 ) 5 NH 3 ]ZnCl 4 crystals were investigated using X-ray diffraction (XRD), Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), thermogravimetric analysis, and nuclear magnetic resonance (NMR). The crystals at 300 K had a monoclinic structure with C2/c space group and lattice constants are a = 21.4175 Å, b = 7.3574 Å, c = 19.1079 Å, β = 120.5190°, and Z = 8. Three endothermic peaks at 256, 390, and 481 K were observed in the DSC curve. From the single-crystal XRD patterns, powder XRD patterns, and optical microscopy results based on the temperature change, the phase transition and melting temperatures were determined to be 390 and 481 K, respectively. NMR studies indicated no change in 1 H chemical shifts, but a change in the chemical shifts for C2, located between C1 and C3 of the cation at 340 K. Increase in molecular motion caused an increase in the spin-lattice relaxation time, T 1ρ , at low spinning rates, under magic-angle spinning rate conditions. This crystal showed a minor change in the N-H···Cl hydrogen bond, related to the coordination geometry of the ZnCl 4 anion., (© 2022. The Author(s).)

Purpose: First-line choice of therapy is critical as it affects treatment decisions in later lines in patients with metastatic colorectal cancer (mCRC). We assessed changes in renal function for 1 year among patients diagnosed with mCRC who received first-line chemotherapy. We aimed to analyze the prognostic factors and effect of each chemotherapy regimen on the renal function of the patients., Methods: We retrospectively investigated patients with mCRC who were treated with a standard triplet regimen (FOLFOX/FOLFIRI with bevacizumab/cetuximab) in the first-line setting at Korea University Anam Hospital from 2015 to 2020. We checked renal function at 3-month intervals for 12 months. We calculated changes in eGFR (△eGFR, estimated glomerular filtration rate) and compared them with clinical factors such as age, sex, chronic disease, body mass index (BMI), disease status, baseline proteinuria, and first-line chemotherapy regimen., Results: Among 472 patients with mCRC, the median eGFR at baseline was 90.9 mL/min/1.73 m 2 ; it was significantly lower (80.1 mL/min/1.73 m 2 , p < 0.001) at 12 months after chemotherapy initiation. Particularly, the eGFR of patients treated with FOLFIRI + bevacizumab was 74.9 mL/min/1.73 m 2 . The 1-year incidence rate of acute kidney injury (AKI) was 9.1%, with the lowest occurrence in patients receiving FOLFOX/cetuximab (2.1%) and the highest in those receiving FOLFIRI + bevacizumab (19.2%). Renal dysfunction was more frequent with FOLFIRI + bevacizumab as compared to the other regimens. Additionally, old age, low BMI, and proteinuria at baseline were also associated with a decreased eGFR., Conclusions: These findings can serve as important factors when selecting the first-line chemotherapy regimen for patients with mCRC., (© 2022. The Author(s).)

This study aimed to identify novel biomarkers for metastatic colorectal cancer progression using exosomal RNA expression profiling. The exosomal RNA expression profiles of 54 patients with mCRC were investigated. Exosomal RNA profiling was performed at the time of relapse immediately before metastasectomy and cancer recurrence or progression after metastasectomy. The up- and down-regulated RNA expression profiles were screened and analyzed using H-cluster, principle component analysis and gene ontology. The tissue expression profile of the liver metastases was compared with the GSE 41258 set using GSEA tools. We identified two distinctive biological process gene sets (IFNA and PCDB families) related to metastatic progression. The interferon-α response gene set was enriched, especially when the tumor volume was ≥1 cm 3 . CXCL10, CXCL11 and SAMD 9 mRNA were highly expressed in the plasma exosome samples of patients with mCRC to the liver. Furthermore, high expression of CXCL10 but not CXCL11 or SAMD9 was associated with a poor prognosis and shorter progression-free survival. Conclusions: Cancer-derived exosomal CXCL10 may be a novel biomarker for liver metastasis of mCRC and a potential target for the prevention and treatment of mCRC with liver metastasis.

Organic-inorganic hybrid perovskites have various potential applications in fuel cells and solar cells. In this regard, the physicochemical properties of an organic-inorganic [NH 3 (CH 2 ) 6 NH 3 ]CuCl 4 crystal was conducted. The crystals had a monoclinic structure with space group P 2 1 / n and lattice constants a = 7.2224 Å, b = 7.6112 Å, c = 23.3315 Å, β = 91.930°, and Z = 4 at 300 K, and the phase transition temperature ( T C ) was determined to be 363 K by X-ray diffraction and differential scanning calorimetry experiments. From the nuclear magnetic resonance experimental results, the changes in the 1 H chemical shifts in NH 3 and the influence of C1 located close to NH 3 in the [NH 3 (CH 2 ) 6 NH 3 ] cation near T C are determined to be large, which implies that the structural change of CuCl 4 linked to N-H⋯Cl is large. The 1 H spin-lattice relaxation time ( T 1ρ ) in NH 3 is shorter than that of CH 2 , and the 13 C T 1ρ values for C1 close to NH 3 are shorter than those of C2 and C3 due to the influence of the paramagnetic Cu 2+ ion in square planar geometry CuCl 4 . The structural mechanism for the phase transition was the change in the N-H⋯Cl hydrogen bond and was associated with the structural dynamics of the CuCl 4 anion., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

It is essential to develop novel zero- and two-dimensional hybrid perovskites to facilitate the development of eco-friendly solar cells. In this study, we investigated the structure and dynamics of [NH 3 (CH 2 ) 5 NH 3 ]CuCl 4 via various characterization techniques. Nuclear magnetic resonance (NMR) results indicated that the crystallographic environments of 1 H in NH 3 and 13 C on C3, located close to NH 3 at both ends of the cation, were changed, indicating a large structural change of CuCl 6 connected to N-H···Cl. The thermal properties and structural dynamics of the [NH 3 (CH 2 ) n NH 3 ] cation in [NH 3 (CH 2 ) n NH 3 ]CuCl 4 ( n = 2, 3, 4, and 5) crystals were compared using thermogravimetric analysis (TGA) and NMR results for the methylene chain. The 1 H and 13 C spin-lattice relaxation times (T 1ρ ) exhibited similar trends upon the variation of the methylene chain length, with n = 2 exhibiting shorter T 1ρ values than n = 3, 4, and 5. The difference in T 1ρ values was related to the length of the cation, and the shorter chain length ( n = 2) exhibited a shorter T 1ρ owing to the one closest to the paramagnetic Cu 2+ ions.

Extracellular vesicles (EVs) encompass a wide range of vesicles that are released by all cell types. They package protein, nucleic acids, metabolites, and other cargo that can be delivered to recipient cells and affect their phenotypes. However, little is known about how pharmaceutical agents can alter EV secretion, protein and metabolic cargo, and the active biological processes taking place in these vesicles. In this study, we isolated EVs from human renal cell carcinoma (RCC) cells treated with tyrosine kinase inhibitors (TKIs) Sunitinib and Axitinib. We found these TKIs increase the number of large (lEVs) and small extracellular vesicles (sEVs) secreted from RCC cells in a dose-dependent manner. In addition, quantitative proteomics revealed that metabolic proteins are enriched in sEVs secreted from Sunitinib-treated cells. In particular, the glucose transporter GLUT1 was enriched in sEVs purified from TKI-treated cells. These sEVs displayed increased glucose uptake and glycolytic metabolism compared to sEVs released from vehicle-treated cells. Overexpression of GLUT1 in RCC cells augmented GLUT1 levels in sEVs, which subsequently displayed higher glucose uptake and glycolytic activity. Together, these findings suggest that these TKIs alter metabolic cargo and activity in RCC sEVs., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Purpose: Perioperative blood transfusion in early stage cancer patients had a negative effect on the prognosis of patients, but the prognostic impact of transfusion in advanced cancer patients remains unclear. To minimize and guide rational transfusion, an institutional patient blood management (PBM) program was launched, and we evaluated the new program that has changed the practice and impacted on the prognosis of advanced cancer patients., Methods: We investigated the medical records of colorectal cancer patients who received chemotherapy from 2015 to 2020. The amount and frequency of transfusion, iron replacement and laboratory findings, and overall survival were compared before and after implementation of PBM., Results: The rate of transfusion in colorectal cancer patients was significantly decreased from 23.5/100 person-quarter in 2015 to 1.2/100 person-quarter in 2020, but iron supplementation therapy was frequently used, and the proportion of patients who received transfusion under hemoglobin 7 g/dL significantly increased from 15.9% in 2015 to 55.3% in 2020. Multivariate analysis revealed that transfusion was a significant risk factor affecting the overall survival of patients (HR 2.70, 95% CI: 1.93-3.78, p<0.001). Kaplan-Meier analysis revealed that overall survival was significantly longer in non-transfused patients than in transfused patients (11.0 versus 22.4 months; HR 0.69, 95% CI: 0.56-0.86, p<0.001)., Conclusions: This study shows that minimized transfusion through an institutional PBM can positively affect the prognosis of patients who are receiving chemotherapy for advanced colorectal cancer., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To support the development of eco-friendly hybrid perovskite solar cells, structural, thermal, and physical properties of the lead-free hybrid perovskite [NH 3 (CH 2 ) 3 NH 3 ]CuBr 4 were investigated using X-ray diffraction (XRD), differential scanning calorimetry, thermogravimetric analysis, and nuclear magnetic resonance spectroscopy. The crystal structure confirmed by XRD was monoclinic, and thermodynamic stability was observed at approximately 500 K without any phase transition. The large changes in the 1 H chemical shifts of NH 3 and those in C2 close to N are affected by N-H∙∙∙Br hydrogen bonds because the structural geometry of CuBr 4 changed significantly. The 1 H and 13 C spin-lattice relaxation times (T 1ρ ) showed very similar molecular motions according to the Bloembergen-Purcell-Pound theory at low temperatures; however, the 1 H T 1ρ values representing energy transfer were about 10 times lesser than those of 13 C T 1ρ . Finally, the 1 H and 13 C T 1ρ values of [NH 3 (CH 2 ) 3 NH 3 ]MeBr 4 (Me = Cu, Zn, and Cd) were compared with those reported previously. 1 H T 1ρ was affected by the paramagnetic ion of the anion, while 13 C T 1ρ was affected by the MeBr 4 structure of the anion; 13 C T 1ρ values in Me = Cu and Cd with the octahedral MeBr 6 structure had longer values than those in Me = Zn with the tetrahedral MeBr 4 structure. We believe that these detailed insights on the physical properties will play a crucial role in the development of eco-friendly hybrid perovskite solar cells., (© 2022. The Author(s).)

DNA methylation profiles have been used to develop biomarkers of aging known as epigenetic clocks, which predict chronological age with remarkable accuracy and show promise for inferring health status as an indicator of biological age. Epigenetic clocks were first built to monitor human aging, but their underlying principles appear to be evolutionarily conserved, as they have now been successfully developed for many mammalian species. Here, we describe reliable and highly accurate epigenetic clocks shown to apply to 93 domestic dog breeds. The methylation profiles were generated using the mammalian methylation array, which utilizes DNA sequences that are conserved across all mammalian species. Canine epigenetic clocks were constructed to estimate age and also average time to death. We also present two highly accurate human–dog dual species epigenetic clocks (R = 0.97), which may facilitate the ready translation from canine to human use (or vice versa) of antiaging treatments being developed for longevity and preventive medicine. Finally, epigenome-wide association studies here reveal individual methylation sites that may underlie the inverse relationship between breed weight and lifespan. Overall, we describe robust biomarkers to measure aging and, potentially, health status in canines.

The fundamental principle of precision oncology is centralized on the identification of therapeutically exploitable targets that provides individual patients with cancer an opportunity to make informed decisions on a personalized level. To facilitate and adopt such concepts within clinical practice, we have initiated a nationwide, multi-institutional precision oncology screening program to examine and enroll patients into the most appropriate clinical trial based on their tumor's unique molecular properties. To determine the prevalence of essential major driver mutations and to explore their dynamic associations at both molecular and pathway levels, we present a comprehensive overview on the genomic properties of East Asian patients with cancer. We further delineate the extent of genomic diversity as well as clinical actionability in patients from Western and Eastern cultures at the pan-cancer and single-tumor entity levels. To support fellow oncology communities in future investigations involving large-scale analysis, all data have been made accessible to the public (https://kmportal.or.kr)., Significance: We present a comprehensive overview of molecular properties of East Asian pan-cancer patients and demonstrate significant diversity in terms of genomic characteristics as well as clinical utility compared with patients with European ancestry. The results of this study will lay the groundwork for designing personalized treatments in the clinical setting. See related commentary by Moyers and Subbiah, p. 886. This article is highlighted in the In This Issue feature, p. 873., (©2021 The Authors; Published by the American Association for Cancer Research.)

Organic-inorganic hybrid perovskites can potentially be used in electrochemical devices, such as batteries and fuel cells. In this study, the structure and phase transition temperatures of the organic-inorganic material [NH 3 (CH 2 ) 5 NH 3 ]CdCl 4 crystal were confirmed by X-ray diffraction and differential scanning calorimetry. From the nuclear magnetic resonance results, the crystallographic configurations of 1 H, 13 C, and 14 N in the cation changed at temperatures close to T C1 (336 K), whereas that of 113 Cd in the anion shows significant changes at temperatures close to T C1 and T C2 (417 K). The activation energy, E a , values for 1 H and 13 C obtained from the spin-lattice relaxation time, T 1ρ , below and above T C1 were evaluated, where the E a value for 13 C was more flexible at low temperatures than at high temperatures. In addition, the effect on molecular motion was effective at high temperatures. The phase transition at 336 K was associated with the change in the N-H···Cl bond due to the change in the coordination geometry of Cl around Cd in the CdCl 6 anion. On the other hand, the phase transition at 417 K was related to the ferroelastic phase transition attributed to the twin domains., (© 2022. The Author(s).)

Purpose: K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods., Materials and Methods: Colorectal, breast, non-small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non-small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers)., Results: In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively., Conclusion: The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.

Although dormancy is thought to play a key role in the metastasis of breast tumor cells to the brain, our knowledge of the molecular mechanisms regulating disseminated tumor cell (DTC) dormancy in this organ is limited. Here using serial intravital imaging of dormant and metastatic triple-negative breast cancer lines, we identify escape from the single-cell or micrometastatic state as the rate-limiting step towards brain metastasis. We show that every DTC occupies a vascular niche, with quiescent DTCs residing on astrocyte endfeet. At these sites, astrocyte-deposited laminin-211 drives DTC quiescence by inducing the dystroglycan receptor to associate with yes-associated protein, thereby sequestering it from the nucleus and preventing its prometastatic functions. These findings identify a brain-specific mechanism of DTC dormancy and highlight the need for a more thorough understanding of tumor dormancy to develop therapeutic approaches that prevent brain metastasis., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Disseminated tumor cells (DTCs) spread systemically yet distinct patterns of metastasis indicate a range of tissue susceptibility to metastatic colonization. Distinctions between permissive and suppressive tissues are still being elucidated at cellular and molecular levels. Although there is a growing appreciation for the role of the microenvironment in regulating metastatic success, we have a limited understanding of how diverse tissues regulate DTC dormancy, the state of reversible quiescence and subsequent awakening thought to contribute to delayed relapse. Several themes of microenvironmental regulation of dormancy are beginning to emerge, including vascular association, co-option of pre-existing niches, metabolic adaptation, and immune evasion, with tissue-specific nuances. Conversely, DTC awakening is often associated with injury or inflammation-induced activation of the stroma, promoting a proliferative environment with DTCs following suit. We review what is known about tissue-specific regulation of tumor dormancy on a tissue-by-tissue basis, profiling major metastatic organs including the bone, lung, brain, liver, and lymph node. An aerial view of the barriers to metastatic growth may reveal common targets and dependencies to inform the therapeutic prevention of relapse., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The structure of organic-inorganic perovskite [NH 3 (CH 2 ) 4 NH 3 ]ZnCl 4 was determined; the lattice constants with monoclinic structure were determined to be a = 7.2527 Å, b = 8.1101 Å, c = 10.3842 Å, and β = 80.3436°. The crystal was almost thermally stable up to approximately 560 K. The endothermic peaks at 481 K and 506 K were assigned to the phase transition of the material. In addition, the structural characteristics and molecular dynamics of the cation were studied via magic angle spinning nuclear magnetic resonance experiments. Based on the results, the effects of the length of the CH 2 group in the cation of the [NH 3 (CH 2 ) n NH 3 ]ZnCl 4 ( n = 2, 3, and 4) crystals were considered. Regardless of whether n was even or odd, the differences in the thermal and physical properties were minimal. Moreover, a difference in molecular motion relative to the length of the cation was observed only at high temperatures. These results provide useful information about the thermal stability and molecular dynamics of [NH 3 (CH 2 ) n NH 3 ]ZnCl 4 crystals and are expected to facilitate potential applications of such compounds in supercapacitors, batteries, and fuel cells., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Hybrid perovskites have potential applications in several electrochemical devices such as supercapacitors, batteries, and fuel cells. Here, the thermal stabilities as a function of the length n of the CH 2 groups in [NH 3 (CH 2 ) n NH 3 ]CdCl 4 ( n = 2, 3, and 4) crystals were considered by TGA and DTA. The structural characteristics and molecular dynamics were studied by MAS and static NMR experiments. A comparison of spin-lattice relaxation times indicated that the organic cation containing 1 H and 13 C was significantly more flexible than the inorganic anion containing 113 Cd. The flexibility of 1 H increased with an increase in the length of CH 2 in the carbon chain, resulting in a decrease in the activation energy ( E a ) of 1 H. The E a of 13 C at n = 3 and 4 was more flexible at high temperatures than at low temperatures. In contrast, the E a of 13 C at n = 2 was more flexible at low temperatures. These results provide insight into the thermal stability and molecular dynamics of these crystals as a function of the length n of CH 2 groups in the carbon chain and are expected to facilitate applications., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)